AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired f...AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS:TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simulta-neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy. CONCLUSION:TXN and TXNIP are promising prognostic markers for gastric cancer, and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.展开更多
This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Da...This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECⅡ were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O2/5% CO2 and those in the air group to 95% air/5% CO2. After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species （ROS）, apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AECⅡ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group （P0.001）. Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group （P0.001）. RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECⅡ exposed to hyperoxia for 12 and 24 h （P0.01）, respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group （P0.05）. Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECⅡ in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.展开更多
Ribonucleotide reductase(RNR), the rate-limitingenzyme in DNA synthesis, catalyzes reduction of thedifferent ribonucleotides to their corresponding deoxyri-bonucleotides. The crucial role of RNR in DNA synthesishas ma...Ribonucleotide reductase(RNR), the rate-limitingenzyme in DNA synthesis, catalyzes reduction of thedifferent ribonucleotides to their corresponding deoxyri-bonucleotides. The crucial role of RNR in DNA synthesishas made it an important target for the development ofantiviral and anticancer drugs. Taking account of the re-cent developments in this field of research, this reviewfocuses on the role of thioredoxin and glutaredoxin sys-tems in the redox reactions of the RNR catalysis.展开更多
Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk ...Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.展开更多
Thioredoxin (Trx) is a small ubiquitous dithiol protein which together with the FADcontaining enzyme thioredoxin reductase (TR) and NADPH (the Trx system) is a hydrogen donor for ribonucleotide reductase essential for...Thioredoxin (Trx) is a small ubiquitous dithiol protein which together with the FADcontaining enzyme thioredoxin reductase (TR) and NADPH (the Trx system) is a hydrogen donor for ribonucleotide reductase essential for DNA synthesis and a general protein disulfide reductase involved in redox regulation. Selenite, selenodiglutathione (GS-Se-SG) and selenocystine are efficiently reduced by thioredoxins and also directly by NADPH and mammalian TR but not by the E. coli enzyme. Incubation of selenite or GS-Se-SG with the Trx system or with mammalian TR results in a rapid formation of selenide, which by redox cycling with oxygen may cause a large non-stoichiometric oxidation of NADPH. Selenocystine is efficiently reduced into two molecules of the selenol amino acid selenocysteine by mammalian TR with a Km-value (6μmol·L-1 ) and a high turnover number (kcat, 3200 min-1) almost identical to the natural substrate Trx-S2. TR also directly reduces lipid hydroperoxides and this peroxidase reaction is strongly stimulated by the presence of catalytic amounts of free selenocysteine. Glutaredoxin (Grx) which catalyzes GSH dependent disulfide reduction also via a redox-active disulfide and Trx are both efficient electron donors to the hut-nan plasrna glutathione peroxidase providing a mechanism by which human plasma glutathione peroxidase may reduce hydroperoxides in an environment almost free from glutathione. Selenate is reduced by Grx and Trx in the presence of GSH. The DNA-binding of the transcription factor AP-1 is strongly inhibited by GS-Se-SG and selenite. Furtherrnore, selenide formed by TR-mediated reduction of selenite and GS-Se-SG inhibits lipoxygenase and changes the electron spin resonance spectrum of the active site iron. Mammalian TR with two subunits of 57 kDa has recently been cloned and shown to be homologous to glutathione reductase. The rat enzyme contains a selenocysteine residue in a unique Cterminal position and a conserved SEClS sequence directing insertion of the selenocysteine. The discovery of selenocysteine in mammalian TR may explain the broad substrate specificity of the enzyme and the requirement of seleflium for cell proliferation展开更多
Objective To investigate the possible effect of artesunate （ART） on schistosome thioredoxin glutathione reductase （TGR） and cytochrome c peroxidase （CcP） in Schistosoma mansoni-infected mice. Methods A total of ...Objective To investigate the possible effect of artesunate （ART） on schistosome thioredoxin glutathione reductase （TGR） and cytochrome c peroxidase （CcP） in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups （50 mice in each group）. Group I： infected untreated group （Control group） received a vehicle of 1% sodium carbonyl methylcellulose （CMC-Na）; Group II： infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV： infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance （100%） of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.展开更多
Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigat...Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.展开更多
We aimed to investigate the role of thioredoxin reductase （TR） and inducible heat shock protein 70 （iHsp70） and their relationship with sperm quality in varicocele （VAR） patients. Semen samples were obtained fro...We aimed to investigate the role of thioredoxin reductase （TR） and inducible heat shock protein 70 （iHsp70） and their relationship with sperm quality in varicocele （VAR） patients. Semen samples were obtained from 16 subfertile men diagnosed as VAR and 10 fertile men who applied to the Andrology Laboratory of Istanbul Medical Faculty of Istanbul University. The sperm TR and iHsp 70 expression levels were determined using Western blot analysis. The TR activity of the sperm was assayed spectrophometrically. The sperm quality was evaluated both by conventional sperm analysis and by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） technique that assayed DNA-fragmented spermatozoa in semen samples. The percentage of TUNELopositive spermatozoa in the VAR group （16.3%±5.6%） was higher than that in the fertile group （5.5%±1.9%）. Significant inverse correlations were detected between the percentage of TUNEL-positive cells and both the concentration （r=--0.609; P=0.001） and motility （r=--0.550; P=-0.004） of spermatozoa. Both the TR expression and activity were increased significantly in the VAR group （U=22.0; P=0.001 and U=33.5 P=0.012, respectively） as analyzed using the Mann-Whitney UWilcoxon rank sum Wtest. Furthermore, significant positive correlations were found between TR expression and activity （r=-0.406; P=O.040） and between TR expression and the percentage of TUNEL-positive cells （r=0.665; P=-0.001）. Sperm iHsp70 expression did not differ between the VAR and fertile groups. In conclusion, increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with VAR.展开更多
Objective:To explore the regulatory role of thioredoxin-interacting protein(TXNIP) in Wnt/β-catenin signaling pathway and therefore to elucidate its function in diabetic myocardial infarction.Methods:Diabetic myocard...Objective:To explore the regulatory role of thioredoxin-interacting protein(TXNIP) in Wnt/β-catenin signaling pathway and therefore to elucidate its function in diabetic myocardial infarction.Methods:Diabetic myocardial infarction models were generated in mice.The expression levels of TXNIP and β-catenin and level of reactive oxygen species(ROS) were determined and compared with those in control group.Human umbilical vein endothelial cells were treated with high-eoncentration glucose and/or silencing TXNIP and/or H_2O_2.After 24 h,expression levels of TXNIP、β-catenin and its downstream protein Cyclin D1,and C-myc gene were determined by real-time PCR,Western blot and immunofluorescence method.The cell proliferation and ROS production capability in different groups were determined by methyl thiazolyl tetrazolium assay.Results:Compared with control group,hyperglycemia significantly up-regulated TXNIP expression and ROS level in the myocardium and endothelial cells of myocardial infarction area,whereas the β-catenin expression was down-regulated,and the difference was statistically significant(P<0.05).In comparison with Human umbilical vein endothelial cells in the control group,high glucose level increased the levels of TXNIP expression and ROS level in cells,but reduced cell proliferation as well as migration capability and expression levels of β-catenin,Cyclin D1 and C-myc;the difference was statistically significant(P<0.05).However,this trend can be partially reversed by silencing TXNIP.Conclusions:Diabetic myocardial ischemia could up-regulate levels of TXNIP expression and ROS production in endothelial cells of myocardial infarction area.The regulation effect of TXNIP on β-catenin was partially achieved by changing ROS levels.展开更多
AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima...AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study.All patients had chronic liver disease(CLD) due to infection with HCV.Thirty patients with HCV-related HCC,34 with HCV-related CLD without HCC(non-HCC),and 20 healthy volunteers(HVs) were enrolled.Possible associations between serum manganese superoxide dismutase(MnSOD) and thioredoxin(TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo.RESULTS:The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.03) or HVs(P < 0.001).Similarly,serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.04) or HVs(P < 0.01).However,serum levels of MnSOD and TRX were not correlated in patients with HCC.Among patients with HCC,the overall survival rate(OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL(P = 0.01),and the OSR tended to be lower in patients with TRX levels < 80 ng/mL(P = 0.05).In addition,patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL.Furthermore,a multivariate analysis using a Cox proportional hazard model and serum levels of five factors(MnSOD,prothrombin time,serum albumin,serum α-fetoprotein(AFP),and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL(risk ratio:4.12,95% confidential interval:1.22-13.88,P = 0.02) and AFP levels ≥ 40 ng/mL(risk ratio:6.75;95% confidential interval:1.70-26.85,P < 0.01) were independent risk factors associated with a poor patient prognosis.CONCLUSION:Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC.展开更多
Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affin...Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE （FcεRI） was significantly suppressed in TRX transgenic （TRX-tg） mice compared to wild type （WT） mice. Intracellular reactive oxygen species （ROS） of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production ofcytokines （IL-6 and TNF-α） from mast cells in response to 2,4-dinitrophenylated bovine serum albumin （DNP-BSA） stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper （Th） 2 dominant in primary immune response, although there was no difference in the population of dendritic cells （DCs） and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.展开更多
Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thiore...Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.展开更多
Human thioredoxin and antibacterial peptide, PR39, have been shown to have potent antioxidant effects that may prolong survival of cells during hypoxia. The pSSCMV/human thioredoxin-PR39 vector was successfully constr...Human thioredoxin and antibacterial peptide, PR39, have been shown to have potent antioxidant effects that may prolong survival of cells during hypoxia. The pSSCMV/human thioredoxin-PR39 vector was successfully constructed in this study and used to infect ECV304 cells. Transfected ECV304 cells were incubated at 1%, 5% hypoxic, and normal oxygen conditions. We found that the number of apoptotic cells after transfection with recombinant adeno-associated virus-human thioredoxin -PR39 was significantly lower than controls, suggesting a protective effect of the recombinant human thioredoxin-PR39 protein on hypoxic cells.展开更多
Objective To clone and determine the sequence and expression of a cDNA segment for human thioredoxin. Methods The cDNA segment of thioredoxin was obtained through amplification by RT PCR cloning from 143 (TK -) hu...Objective To clone and determine the sequence and expression of a cDNA segment for human thioredoxin. Methods The cDNA segment of thioredoxin was obtained through amplification by RT PCR cloning from 143 (TK -) human osteosarcoma cell. The amplified products were cloned into pGEM T Easy vector and sequenced. Then the expressed vector pBV220 hTRX was constructed and transformed into E.coli strain DH5α for hTRX expression. The hTRX was purified by DEAE Sephadex A 50 column and the activity of recombinant hTRX was determined by the insulin disulfide reduction assay. Results Comparison of cDNA sequence of the cloned fragments with that of the reported hTRX (GenBank J04026) demonstrated that there were two differences compared to the reported cDNA sequence for hTRX at bp180 and bp284, and the amino acids enceoded altered respectively, but motif of the sequence was identical to that of the reported hTRX. The recombinant hTRX can catalyze insulin reduction by DTT. Conclusion The successful cloning and expression of hTRX cDNA formed a basis for further study on biological functions and utilization of hTRX.展开更多
Thioredoxin （Trx） proteins are involved in many biological processes especially the regulation of cellular redox homeostasis. In this study, two Trx cDNAs were cloned from the mussel Mytilus galloprovincialis using ...Thioredoxin （Trx） proteins are involved in many biological processes especially the regulation of cellular redox homeostasis. In this study, two Trx cDNAs were cloned from the mussel Mytilus galloprovincialis using rapid amplification of cDNA ends-polymerase chain reaction （RACE-PCR）. The two cDNAs were named MgTrxl and MgTrx2, respectively. The open reading frames of MgTrxl and MgTrx2 were 318 and 507 base pairs （bp） and they encoded proteins of 105 and 168 amino acids with estimated molecular masses of 11.45 and 18.93 kDa, respectively. Sequence analysis revealed that both proteins possessed the conserved active site dithiol motif Cys-Gly-Pro-Cys. In addition, MgTrx2 also possessed a putative mitochondrial targeting signal suggesting that it is located in the mitochondria. Quantitative real-time polymerase chain reaction （qPCR） revealed that both MgTrxl and MgTrx2 were constitutively expressed in all tissues examined. The MgTrxl transcript was most abundant in hemocytes and gills, whereas the MgTrx2 transcript was most abundant in gonad, hepatopancreas, gill and hemocytes. Following Vibrio anguillarum challenge, the expression of MgTrxl was up-regulated and reached its peak, at a value 10-fold the initial value, at 24 h. Subsequently, expression returned back to the original level. In contrast, the expression level of MgTrx2 was down-regulated following bacterial stimulation, with one fifth of the control level evident at 12 h post challenge. These results suggest that MgTrxl and MgTrx2 may play important roles in the response ofM. galloprovincialis to bacterial challenge.展开更多
Varying degrees of central systemneurolopathic involvement induced by diabetes mellitus(DM)contributes to cognitive decline,is known as diabetic encephalopathy(DE),which is also one of the independent risk factors of ...Varying degrees of central systemneurolopathic involvement induced by diabetes mellitus(DM)contributes to cognitive decline,is known as diabetic encephalopathy(DE),which is also one of the independent risk factors of Alzheimer's disease(AD).This study aims to investigate whether thioredoxin(Trx)could alleviate DE and AD through endoplasmic reticulum stress(ERS),antioxidant stress and apoptosis signaling pathway.展开更多
Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a re...Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a redox regulating protein,and plays roles in resisting the oxidative stress and protecting neurons. Our previous study found that Trx-1 improved the cognitive function of Parkinson’s Disease( PD) mice. Geranylgeranylacetone( GGA) is an antiulcer drug and induces the expression of Trx-1 in vivo and in vitro. However,whether Trx-1 improves cognitive functions in mice of APP/PS1 or GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ is still unknown. The objective of present is to investigate the roles of Trx-1 and GGA in inhibiting neurotoxicity of Aβ. Methods:We used MTT assay to test the cell viability induced by Aβ(25-35) and western blot to detect the expression of Trx-1 in SH-SY5 Y cells. Trx-1 overexpression transgenic mice were hybridized with APP/PS1 transgenic mice to get control,Trx-1,Tx-1/APP/PS1 and APP/PS1 mice. Then we used Morris water maze,high plus maze and object recognition test to detect the cognitive function of different kinds of mice. We also used RT-PCR and western blot to test the mRNA level and expression of Trx-1,APP,PS1 and Aβ. Results:In our present study,we demonstrated that Aβ(25-35) decreased the cell viability and the expression of Trx-1 in SH-SY5 Y cells. The cell viability and the expression of Trx-1 were reversed by GGA. Our results showed that the escape latency in APP/PS1 mice was longer when compared with the Trx-1/APP/PS1 mice in Morris water maze and high plus maze. Whereas navigational experiments in Morris water maze result showed that the total number of crossings and the percentage of time spent in the target quadrant were significantly decreased in APP/PS1 mice when compared to Trx-1/APP/PS1 mice. Object recognition test the discrimination index was significantly decreased in APP/PS1 mice when compared with Trx-1/APP/PS1 mice. The mRNA levels and the expression of APP,PS1 and Aβ were decreased in Trx-1/APP/PS1 mice when compared to APP/PS1 mice. Conclusion:These results suggest that GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ(25-35) and restored the expression of Trx-1. Trx-1 overexpression improves cognitive function of APP/PS1 mice. Trx-1 may be a potential therapeutic target for the clinical management of AD.展开更多
基金Supported by The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, No. 2010-0024248A Faculty Research Grant from Yonsei University College of Medicine for 2011, No. 6-2011-0113, 6-2011-0146
文摘AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS:TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simulta-neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy. CONCLUSION:TXN and TXNIP are promising prognostic markers for gastric cancer, and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30770944)
文摘This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 （Trx1） and thioredoxin reductase-1 （TrxR1） in alveolar type Ⅱ epithelial cells （AECⅡ） of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECⅡ were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O2/5% CO2 and those in the air group to 95% air/5% CO2. After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species （ROS）, apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AECⅡ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group （P0.001）. Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group （P0.001）. RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECⅡ exposed to hyperoxia for 12 and 24 h （P0.01）, respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group （P0.05）. Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECⅡ in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.
基金Supported by The Swedish Research Council Medicine,No.3529The Swedish Cancer Society,No.961The Wallenberg Foundation
文摘Ribonucleotide reductase(RNR), the rate-limitingenzyme in DNA synthesis, catalyzes reduction of thedifferent ribonucleotides to their corresponding deoxyri-bonucleotides. The crucial role of RNR in DNA synthesishas made it an important target for the development ofantiviral and anticancer drugs. Taking account of the re-cent developments in this field of research, this reviewfocuses on the role of thioredoxin and glutaredoxin sys-tems in the redox reactions of the RNR catalysis.
文摘Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.
文摘Thioredoxin (Trx) is a small ubiquitous dithiol protein which together with the FADcontaining enzyme thioredoxin reductase (TR) and NADPH (the Trx system) is a hydrogen donor for ribonucleotide reductase essential for DNA synthesis and a general protein disulfide reductase involved in redox regulation. Selenite, selenodiglutathione (GS-Se-SG) and selenocystine are efficiently reduced by thioredoxins and also directly by NADPH and mammalian TR but not by the E. coli enzyme. Incubation of selenite or GS-Se-SG with the Trx system or with mammalian TR results in a rapid formation of selenide, which by redox cycling with oxygen may cause a large non-stoichiometric oxidation of NADPH. Selenocystine is efficiently reduced into two molecules of the selenol amino acid selenocysteine by mammalian TR with a Km-value (6μmol·L-1 ) and a high turnover number (kcat, 3200 min-1) almost identical to the natural substrate Trx-S2. TR also directly reduces lipid hydroperoxides and this peroxidase reaction is strongly stimulated by the presence of catalytic amounts of free selenocysteine. Glutaredoxin (Grx) which catalyzes GSH dependent disulfide reduction also via a redox-active disulfide and Trx are both efficient electron donors to the hut-nan plasrna glutathione peroxidase providing a mechanism by which human plasma glutathione peroxidase may reduce hydroperoxides in an environment almost free from glutathione. Selenate is reduced by Grx and Trx in the presence of GSH. The DNA-binding of the transcription factor AP-1 is strongly inhibited by GS-Se-SG and selenite. Furtherrnore, selenide formed by TR-mediated reduction of selenite and GS-Se-SG inhibits lipoxygenase and changes the electron spin resonance spectrum of the active site iron. Mammalian TR with two subunits of 57 kDa has recently been cloned and shown to be homologous to glutathione reductase. The rat enzyme contains a selenocysteine residue in a unique Cterminal position and a conserved SEClS sequence directing insertion of the selenocysteine. The discovery of selenocysteine in mammalian TR may explain the broad substrate specificity of the enzyme and the requirement of seleflium for cell proliferation
文摘Objective To investigate the possible effect of artesunate （ART） on schistosome thioredoxin glutathione reductase （TGR） and cytochrome c peroxidase （CcP） in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups （50 mice in each group）. Group I： infected untreated group （Control group） received a vehicle of 1% sodium carbonyl methylcellulose （CMC-Na）; Group II： infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV： infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance （100%） of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.
基金Project (No.30472036) supported by the National Natural Science Foundation of China
文摘Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone)ethane (BBSKE),a novel TrxR inhibitor,were investigated on human leu-kemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to inves-tigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.
文摘We aimed to investigate the role of thioredoxin reductase （TR） and inducible heat shock protein 70 （iHsp70） and their relationship with sperm quality in varicocele （VAR） patients. Semen samples were obtained from 16 subfertile men diagnosed as VAR and 10 fertile men who applied to the Andrology Laboratory of Istanbul Medical Faculty of Istanbul University. The sperm TR and iHsp 70 expression levels were determined using Western blot analysis. The TR activity of the sperm was assayed spectrophometrically. The sperm quality was evaluated both by conventional sperm analysis and by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） technique that assayed DNA-fragmented spermatozoa in semen samples. The percentage of TUNELopositive spermatozoa in the VAR group （16.3%±5.6%） was higher than that in the fertile group （5.5%±1.9%）. Significant inverse correlations were detected between the percentage of TUNEL-positive cells and both the concentration （r=--0.609; P=0.001） and motility （r=--0.550; P=-0.004） of spermatozoa. Both the TR expression and activity were increased significantly in the VAR group （U=22.0; P=0.001 and U=33.5 P=0.012, respectively） as analyzed using the Mann-Whitney UWilcoxon rank sum Wtest. Furthermore, significant positive correlations were found between TR expression and activity （r=-0.406; P=O.040） and between TR expression and the percentage of TUNEL-positive cells （r=0.665; P=-0.001）. Sperm iHsp70 expression did not differ between the VAR and fertile groups. In conclusion, increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with VAR.
基金Supported by Fund Project.National Natural Science Foundation of China with Grant No.81500290
文摘Objective:To explore the regulatory role of thioredoxin-interacting protein(TXNIP) in Wnt/β-catenin signaling pathway and therefore to elucidate its function in diabetic myocardial infarction.Methods:Diabetic myocardial infarction models were generated in mice.The expression levels of TXNIP and β-catenin and level of reactive oxygen species(ROS) were determined and compared with those in control group.Human umbilical vein endothelial cells were treated with high-eoncentration glucose and/or silencing TXNIP and/or H_2O_2.After 24 h,expression levels of TXNIP、β-catenin and its downstream protein Cyclin D1,and C-myc gene were determined by real-time PCR,Western blot and immunofluorescence method.The cell proliferation and ROS production capability in different groups were determined by methyl thiazolyl tetrazolium assay.Results:Compared with control group,hyperglycemia significantly up-regulated TXNIP expression and ROS level in the myocardium and endothelial cells of myocardial infarction area,whereas the β-catenin expression was down-regulated,and the difference was statistically significant(P<0.05).In comparison with Human umbilical vein endothelial cells in the control group,high glucose level increased the levels of TXNIP expression and ROS level in cells,but reduced cell proliferation as well as migration capability and expression levels of β-catenin,Cyclin D1 and C-myc;the difference was statistically significant(P<0.05).However,this trend can be partially reversed by silencing TXNIP.Conclusions:Diabetic myocardial ischemia could up-regulate levels of TXNIP expression and ROS production in endothelial cells of myocardial infarction area.The regulation effect of TXNIP on β-catenin was partially achieved by changing ROS levels.
基金Supported by (in part) Grants from the Ministry of Education,Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labour and Welfare of Japan
文摘AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study.All patients had chronic liver disease(CLD) due to infection with HCV.Thirty patients with HCV-related HCC,34 with HCV-related CLD without HCC(non-HCC),and 20 healthy volunteers(HVs) were enrolled.Possible associations between serum manganese superoxide dismutase(MnSOD) and thioredoxin(TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo.RESULTS:The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.03) or HVs(P < 0.001).Similarly,serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.04) or HVs(P < 0.01).However,serum levels of MnSOD and TRX were not correlated in patients with HCC.Among patients with HCC,the overall survival rate(OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL(P = 0.01),and the OSR tended to be lower in patients with TRX levels < 80 ng/mL(P = 0.05).In addition,patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL.Furthermore,a multivariate analysis using a Cox proportional hazard model and serum levels of five factors(MnSOD,prothrombin time,serum albumin,serum α-fetoprotein(AFP),and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL(risk ratio:4.12,95% confidential interval:1.22-13.88,P = 0.02) and AFP levels ≥ 40 ng/mL(risk ratio:6.75;95% confidential interval:1.70-26.85,P < 0.01) were independent risk factors associated with a poor patient prognosis.CONCLUSION:Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC.
文摘Thioredoxin-1 （TRX） is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE （FcεRI） was significantly suppressed in TRX transgenic （TRX-tg） mice compared to wild type （WT） mice. Intracellular reactive oxygen species （ROS） of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production ofcytokines （IL-6 and TNF-α） from mast cells in response to 2,4-dinitrophenylated bovine serum albumin （DNP-BSA） stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper （Th） 2 dominant in primary immune response, although there was no difference in the population of dendritic cells （DCs） and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.
文摘Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.
基金sponsored by the National Natural Science Foundation of China,No.30970992
文摘Human thioredoxin and antibacterial peptide, PR39, have been shown to have potent antioxidant effects that may prolong survival of cells during hypoxia. The pSSCMV/human thioredoxin-PR39 vector was successfully constructed in this study and used to infect ECV304 cells. Transfected ECV304 cells were incubated at 1%, 5% hypoxic, and normal oxygen conditions. We found that the number of apoptotic cells after transfection with recombinant adeno-associated virus-human thioredoxin -PR39 was significantly lower than controls, suggesting a protective effect of the recombinant human thioredoxin-PR39 protein on hypoxic cells.
文摘Objective To clone and determine the sequence and expression of a cDNA segment for human thioredoxin. Methods The cDNA segment of thioredoxin was obtained through amplification by RT PCR cloning from 143 (TK -) human osteosarcoma cell. The amplified products were cloned into pGEM T Easy vector and sequenced. Then the expressed vector pBV220 hTRX was constructed and transformed into E.coli strain DH5α for hTRX expression. The hTRX was purified by DEAE Sephadex A 50 column and the activity of recombinant hTRX was determined by the insulin disulfide reduction assay. Results Comparison of cDNA sequence of the cloned fragments with that of the reported hTRX (GenBank J04026) demonstrated that there were two differences compared to the reported cDNA sequence for hTRX at bp180 and bp284, and the amino acids enceoded altered respectively, but motif of the sequence was identical to that of the reported hTRX. The recombinant hTRX can catalyze insulin reduction by DTT. Conclusion The successful cloning and expression of hTRX cDNA formed a basis for further study on biological functions and utilization of hTRX.
基金Supported by the National Natural Science Foundation of China(No.31172388)the 100 Talents Program of the Chinese Academy of Sciencesthe Key Laboratory for Ecological Environment in Coastal Areas(201011),State Oceanic Administration
文摘Thioredoxin （Trx） proteins are involved in many biological processes especially the regulation of cellular redox homeostasis. In this study, two Trx cDNAs were cloned from the mussel Mytilus galloprovincialis using rapid amplification of cDNA ends-polymerase chain reaction （RACE-PCR）. The two cDNAs were named MgTrxl and MgTrx2, respectively. The open reading frames of MgTrxl and MgTrx2 were 318 and 507 base pairs （bp） and they encoded proteins of 105 and 168 amino acids with estimated molecular masses of 11.45 and 18.93 kDa, respectively. Sequence analysis revealed that both proteins possessed the conserved active site dithiol motif Cys-Gly-Pro-Cys. In addition, MgTrx2 also possessed a putative mitochondrial targeting signal suggesting that it is located in the mitochondria. Quantitative real-time polymerase chain reaction （qPCR） revealed that both MgTrxl and MgTrx2 were constitutively expressed in all tissues examined. The MgTrxl transcript was most abundant in hemocytes and gills, whereas the MgTrx2 transcript was most abundant in gonad, hepatopancreas, gill and hemocytes. Following Vibrio anguillarum challenge, the expression of MgTrxl was up-regulated and reached its peak, at a value 10-fold the initial value, at 24 h. Subsequently, expression returned back to the original level. In contrast, the expression level of MgTrx2 was down-regulated following bacterial stimulation, with one fifth of the control level evident at 12 h post challenge. These results suggest that MgTrxl and MgTrx2 may play important roles in the response ofM. galloprovincialis to bacterial challenge.
文摘Varying degrees of central systemneurolopathic involvement induced by diabetes mellitus(DM)contributes to cognitive decline,is known as diabetic encephalopathy(DE),which is also one of the independent risk factors of Alzheimer's disease(AD).This study aims to investigate whether thioredoxin(Trx)could alleviate DE and AD through endoplasmic reticulum stress(ERS),antioxidant stress and apoptosis signaling pathway.
文摘Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a redox regulating protein,and plays roles in resisting the oxidative stress and protecting neurons. Our previous study found that Trx-1 improved the cognitive function of Parkinson’s Disease( PD) mice. Geranylgeranylacetone( GGA) is an antiulcer drug and induces the expression of Trx-1 in vivo and in vitro. However,whether Trx-1 improves cognitive functions in mice of APP/PS1 or GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ is still unknown. The objective of present is to investigate the roles of Trx-1 and GGA in inhibiting neurotoxicity of Aβ. Methods:We used MTT assay to test the cell viability induced by Aβ(25-35) and western blot to detect the expression of Trx-1 in SH-SY5 Y cells. Trx-1 overexpression transgenic mice were hybridized with APP/PS1 transgenic mice to get control,Trx-1,Tx-1/APP/PS1 and APP/PS1 mice. Then we used Morris water maze,high plus maze and object recognition test to detect the cognitive function of different kinds of mice. We also used RT-PCR and western blot to test the mRNA level and expression of Trx-1,APP,PS1 and Aβ. Results:In our present study,we demonstrated that Aβ(25-35) decreased the cell viability and the expression of Trx-1 in SH-SY5 Y cells. The cell viability and the expression of Trx-1 were reversed by GGA. Our results showed that the escape latency in APP/PS1 mice was longer when compared with the Trx-1/APP/PS1 mice in Morris water maze and high plus maze. Whereas navigational experiments in Morris water maze result showed that the total number of crossings and the percentage of time spent in the target quadrant were significantly decreased in APP/PS1 mice when compared to Trx-1/APP/PS1 mice. Object recognition test the discrimination index was significantly decreased in APP/PS1 mice when compared with Trx-1/APP/PS1 mice. The mRNA levels and the expression of APP,PS1 and Aβ were decreased in Trx-1/APP/PS1 mice when compared to APP/PS1 mice. Conclusion:These results suggest that GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ(25-35) and restored the expression of Trx-1. Trx-1 overexpression improves cognitive function of APP/PS1 mice. Trx-1 may be a potential therapeutic target for the clinical management of AD.
