Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the patients.Although blood glucose ...Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the patients.Although blood glucose control and medications to heart failure show beneficial effects on this disease,there is currently no specific treatment for diabetic cardiomyopathy.Over the past few decades,the pathophysiology of diabetic cardiomyopathy has been extensively studied,and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target.In this review,we summarize the latest research in the field of diabetic cardiomyopathy,focusing on mitochondrial damage and adaptation,altered energy substrates,and potential therapeutic targets.A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.展开更多
Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and...Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.展开更多
Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underly...Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix(ACR)in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease(NAFLD)induced by a high-fat diet(HFD).The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD.Furthermore,ACR ameliorated the dysregulated lipid metabolism in NAFLD mice,as evidenced by reductions in serum triglyceride,total cholesterol,and low-density lipoprotein levels,accompanied by a concomitant increase in the high-density lipoprotein level.ACR treatment also demonstrated a profound anti-oxidative effect,effectively alleviating HFD-induced oxidative stress and promoting ATP production.These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes Ⅰ,Ⅱ,Ⅳ,and Ⅴ,in addition to the activation of the AMPK/PGC-1α pathway,suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism.Moreover,ACR administration mitigated HFD-induced endoplasmic reticulum(ER)stress and suppressed the overexpression of ubiquitin-specific protease 14(USP14)in NAFLD mice.In summary,the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress.These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.展开更多
Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,sub...Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).展开更多
Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly ...Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly divided into a sham-operation group(sham group),a myocardial ischemia reperfusion injury group(MIRI group)and an electroacupuncture pretreatment group(EA group),20 rats in each one.The rats in the sham group and the MIRI group were binded for 7 days,once a day,20 min each time.On the 8th day,the sample was collected after the heart exposed for 50 min in thoractomy in the sham group and the sample was collected after ischemia for 20 min and reperfusion for 30 min in thoractomy in the MIRI group.In the EA group,the pretreatment intervention with electroacupuncture was applied at"Neiguan(内关PC6)","Guanyuan(关元CV4)"and"Zusanli(足三里ST36)"in the rats for 7 days,once a day,20 min each time.On the 8th day,after ischemia for 20 min and reperfusion for 30 min in thoractomy,the sample was collected in the EA group.The changes in STⅡsegment of electroacardiogram(ECG)were observed and measured.Using enzymelinked immunosorbent assay(ELISA),the concentrations of cardiac troponin T(cTnT)and cardiac troponin I(cTnl)were detected.Using nitro blue tetrazolium chloride monohydrate(NBT)staining,the myocardial infarction weight percentage was measured.Using ELISA,the concentrations of mitochondrial adenosine monophosphate(AMP),adenosine diphosphate(ADP)and adenosine triphosphate(ATP)were detected.Results:(1)STⅡchanges:in 20 min of ligation,compared with the sham group,the STⅡsegment of electrocardiograph(ECG)was elevated significantly in the MIRI group and EA group(both P<0.01),but the elevation range in the EA group was lower than that of the MIRI group(P<0.01).After reperfusion for30 min,the STⅡsegment was fallen by over 50%in the MIRI group and the EA group.Simultaneously,the STⅡsegment in the EA group was lower than that of the MIRI group(P<0.01).(2)Regarding myocardial infarction weight percentage,compared with the sham group,the infarction weight was larger in the MIRI group and the EA group(both P<0.05)and the infarction weight in the EA group was lower than that of the MIRI group(P<0.05).(3)Regarding the levels of serum cTnt and cTnI,compared with the sham group,the levels of serum cTnT and cTnI were higher in the MIRI group and the EA group(all P<0.01)and the levels of cTnT and cTnI in the EA group were lower than that of the MIRI group(both P<0.01).(4)Regarding the concentrations of AMP,ADP and ATP,compared with the sham group,ATP concentration was lower in the MIRI group and the EA group(both P<0.01)and the concentrations of AMP and ADP were higher(P<0.05,P<0.01).Compared with the MIRI group,ATP concentration was higher in the EA group(P<0.05)and the concentrations of AMP and ADP were lower(both P<0.01).Conclusions:Electroacupuncture pretreatment reduces the elevation of ECG STⅡsegment,decreases the concentrations of myocardial injury markers,cTnT and cTnI and regulates the transfer among AMP,ATP and ADP.The protective effect of electroacupuncture pretreatment may result from the regulation of mitochondrial energy metabolism.展开更多
Objective:Baoyuan decoction(BYD)is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests.The present study aimed to investigate the effect and mechanism of BYD on ...Objective:Baoyuan decoction(BYD)is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests.The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction(MI).Methods:Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation.Oxygen-glucose deprivation/recovery(OGD/R)model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.Results:BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI.Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.Conclusions:Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways.They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.展开更多
In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cogn...In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM_（2.5） inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice. Furthermore, excessive reactive oxygen species generation was involved in the impairment. Interestingly, these alterations were partially reversed after exposure to PM_（2.5） ended. These findings clarify the mechanism involved in mitochondrial abnormality-related neuropathological dysfunction in response to atmospheric PM_（2.5） inhalation and provide an optimistic sight for alleviating the adverse health outcomes in polluted areas.展开更多
The physiological processes involved in adaptation to osmotic pressure in euryhaline crustaceans are highly energy demanding,but the effects of dietary lipids(fat)on low salinity adaptations have not been well evaluat...The physiological processes involved in adaptation to osmotic pressure in euryhaline crustaceans are highly energy demanding,but the effects of dietary lipids(fat)on low salinity adaptations have not been well evaluated.In the present study,a total of 120 mud crabs(Scylla paramamosain,BW=17.87±1.49 g)were fed control and high-fat(HF)diets,at both medium salinity(23‰)and low salinity(4‰)for 6 wk,and each treatment had 3 replicates with each replicate containing 10 crabs.The results indicated that a HF diet significantly mitigated the reduction in survival rate,percent weight gain and feed efficiency induced by low salinity(P<0.05).Low salinity lowered lipogenesis and activated lipolysis resulting in lipid depletion in the hepatopancreas of mud crabs(P<0.05).Thus,HF diets enhanced the process of lipolysis to supply more energy.In the gills,low salinity and the HF diet increased the levels of mitochondrial biogenesis markers,the activity of mitochondrial complexes,and the expression levels of genes related to energy metabolism(P<0.05).Consequently,the positive effects of the HF diet on energy metabolism in mud crabs at low salinity promoted osmotic pressure regulation.Specifically,significantly higher haemolymph osmotic pressure and inorganic ion content,as well as higher osmotic pressure regulatory enzyme activity in gills,and gene and protein expression levels of NaK-ATPase were observed in crabs fed the HF diet at low salinity(P<0.05).In summary,high dietary lipid levels improved energy provision to facilitate mitochondrial biogenesis,which increased ATP provision for osmotic pressure regulation of mud crabs.This study also illustrates the importance of dietary lipid nutrition supplementation for low salinity adaptations in mud crabs.展开更多
Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation.The circadian rhythmcontrols cell proliferation and energy metabolism.However,the role of circ...Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation.The circadian rhythmcontrols cell proliferation and energy metabolism.However,the role of circadian genes in inflammatory bowel disease is largely unknown.The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism.Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days,whereas those in the control group were not.Subsequently,half of the mice in the control and jet-lagged groups were given dextran sodium sulfate(DSS)to induce colitis.Mice in each group were euthanized at zeitgeber time(ZT)0,ZT4,ZT8,ZT12,ZT16,and ZT20.To investigate the effects of jet lag on the mice,colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes(Bmal1,Clock,Per1,Per2,Cry1,Cry2,and Nr1d1).We analysed the mitochondrial morphology,adenosine triphosphate(ATP)levels,and the expression of dynamin-related protein 1(Drp1)and ser637-phosphorylated(p)-Drp1,which are closely related to ATP production.We further investigated the effect of PER2 knockdown in the colon epithelial cells(CCD 841 CoN)by measuring ATP and cell proliferation levels.Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice,altered the mitochondrial morphology of the colon specimens,decreased the expression of p-Drp1,reduced ATP production,and exacerbated inflammatory responses in mice with DSS-induced colitis.Additionally,silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation.Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.展开更多
基金Yunnan Provincial Cardiovascular Disease Clinical Medical Center Project(Nos.FZX2019-06-01,2022YFKY078)Key Research and Development Program of Sichuan Province(Nos.2022YFS0132,2022YFS0198 and 2023YFS0295)National Natural Science Foundation of China(Nos.81970715 and 82370260)
文摘Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes,which could eventually develop heart failure and leads to the death of the patients.Although blood glucose control and medications to heart failure show beneficial effects on this disease,there is currently no specific treatment for diabetic cardiomyopathy.Over the past few decades,the pathophysiology of diabetic cardiomyopathy has been extensively studied,and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target.In this review,we summarize the latest research in the field of diabetic cardiomyopathy,focusing on mitochondrial damage and adaptation,altered energy substrates,and potential therapeutic targets.A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.
基金Y.Yin including the National Natural Science Foundation of China(82030081 and 81874235)the National Key Research and Development Program of China(2021YFA1300601)the Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project(JCYJ20220818102811024).
文摘Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.
基金supported by the Scientific Research Foundation for the introduction of talent of Pingdingshan University(No.PXY-BSQD-2022040)and Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110055).
文摘Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix(ACR)in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease(NAFLD)induced by a high-fat diet(HFD).The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD.Furthermore,ACR ameliorated the dysregulated lipid metabolism in NAFLD mice,as evidenced by reductions in serum triglyceride,total cholesterol,and low-density lipoprotein levels,accompanied by a concomitant increase in the high-density lipoprotein level.ACR treatment also demonstrated a profound anti-oxidative effect,effectively alleviating HFD-induced oxidative stress and promoting ATP production.These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes Ⅰ,Ⅱ,Ⅳ,and Ⅴ,in addition to the activation of the AMPK/PGC-1α pathway,suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism.Moreover,ACR administration mitigated HFD-induced endoplasmic reticulum(ER)stress and suppressed the overexpression of ubiquitin-specific protease 14(USP14)in NAFLD mice.In summary,the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress.These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.
基金supported by the National Natural Science Foundation of China,Nos.82271222(to ZL),81971012(to ZL),82071189(to XG),and 82201335(to YL)Key Clinical Projects of Peking University Third Hospital,No.BYSYZD2019027(to ZL)。
文摘Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).
基金Supported by National Natural Science Foundation of China Youth Program:81704142Hubei Science and Technology Plan Project:2018CFC890+7 种基金The Twelfth Batch of Self-Selected Research Projects(“Collaborative Innovation”Special Fund):YZ-1845Qihuang Project of National Administration of Traditional Chinese Medicine(National Administration of Traditional Chinese Medicine Yard[2018]:284)Hubei Chinese Medicine Teacher Project(Bulletin of Hubei Health and Family Planning Commission[2018]:15)Hubei Hospital of Traditional Chinese Medicine,the First Tanhualin Famous Doctor,Student Training ProjectHubei Administration of Traditional Chinese Medicine[2018]No.72Wuhan Young and Middle-aged Medical Backbone Talents(Sixth Batch)No.116Family Planning Tong[2018]Young Elite Scientist Sponsors Hip Program by CAST:No.2017QNRC001。
文摘Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly divided into a sham-operation group(sham group),a myocardial ischemia reperfusion injury group(MIRI group)and an electroacupuncture pretreatment group(EA group),20 rats in each one.The rats in the sham group and the MIRI group were binded for 7 days,once a day,20 min each time.On the 8th day,the sample was collected after the heart exposed for 50 min in thoractomy in the sham group and the sample was collected after ischemia for 20 min and reperfusion for 30 min in thoractomy in the MIRI group.In the EA group,the pretreatment intervention with electroacupuncture was applied at"Neiguan(内关PC6)","Guanyuan(关元CV4)"and"Zusanli(足三里ST36)"in the rats for 7 days,once a day,20 min each time.On the 8th day,after ischemia for 20 min and reperfusion for 30 min in thoractomy,the sample was collected in the EA group.The changes in STⅡsegment of electroacardiogram(ECG)were observed and measured.Using enzymelinked immunosorbent assay(ELISA),the concentrations of cardiac troponin T(cTnT)and cardiac troponin I(cTnl)were detected.Using nitro blue tetrazolium chloride monohydrate(NBT)staining,the myocardial infarction weight percentage was measured.Using ELISA,the concentrations of mitochondrial adenosine monophosphate(AMP),adenosine diphosphate(ADP)and adenosine triphosphate(ATP)were detected.Results:(1)STⅡchanges:in 20 min of ligation,compared with the sham group,the STⅡsegment of electrocardiograph(ECG)was elevated significantly in the MIRI group and EA group(both P<0.01),but the elevation range in the EA group was lower than that of the MIRI group(P<0.01).After reperfusion for30 min,the STⅡsegment was fallen by over 50%in the MIRI group and the EA group.Simultaneously,the STⅡsegment in the EA group was lower than that of the MIRI group(P<0.01).(2)Regarding myocardial infarction weight percentage,compared with the sham group,the infarction weight was larger in the MIRI group and the EA group(both P<0.05)and the infarction weight in the EA group was lower than that of the MIRI group(P<0.05).(3)Regarding the levels of serum cTnt and cTnI,compared with the sham group,the levels of serum cTnT and cTnI were higher in the MIRI group and the EA group(all P<0.01)and the levels of cTnT and cTnI in the EA group were lower than that of the MIRI group(both P<0.01).(4)Regarding the concentrations of AMP,ADP and ATP,compared with the sham group,ATP concentration was lower in the MIRI group and the EA group(both P<0.01)and the concentrations of AMP and ADP were higher(P<0.05,P<0.01).Compared with the MIRI group,ATP concentration was higher in the EA group(P<0.05)and the concentrations of AMP and ADP were lower(both P<0.01).Conclusions:Electroacupuncture pretreatment reduces the elevation of ECG STⅡsegment,decreases the concentrations of myocardial injury markers,cTnT and cTnI and regulates the transfer among AMP,ATP and ADP.The protective effect of electroacupuncture pretreatment may result from the regulation of mitochondrial energy metabolism.
基金financially supported by the National Natural Sciences Foundation of China(Nos.81530097 and 81222051)the National Key Technology R&D Program“New Drug Innovation”of China(No.2017ZX09101003-008-003).
文摘Objective:Baoyuan decoction(BYD)is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests.The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction(MI).Methods:Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation.Oxygen-glucose deprivation/recovery(OGD/R)model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.Results:BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI.Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.Conclusions:Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways.They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.
基金supported by the National Science Foundation of China(Nos.21377076,91543203,21477070,21222701)Specialized Research Fund for the Doctoral Program of Higher Education of China(Nos.20121401110003,20131401110005)+1 种基金Project Supported by Shanxi Young Sanjin Scholarship of China,Program for the Outstanding Innovative Teams of Higher Learning Institutions of ShanxiResearch Project Supported by Shanxi Scholarship Council of China(No.2015-006)
文摘In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM_（2.5） inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice. Furthermore, excessive reactive oxygen species generation was involved in the impairment. Interestingly, these alterations were partially reversed after exposure to PM_（2.5） ended. These findings clarify the mechanism involved in mitochondrial abnormality-related neuropathological dysfunction in response to atmospheric PM_（2.5） inhalation and provide an optimistic sight for alleviating the adverse health outcomes in polluted areas.
基金This study was supported by Nature Science Foundation of Zhejiang Province(LY21C190006)the National Natural Science Foundation of China(32072987).
文摘The physiological processes involved in adaptation to osmotic pressure in euryhaline crustaceans are highly energy demanding,but the effects of dietary lipids(fat)on low salinity adaptations have not been well evaluated.In the present study,a total of 120 mud crabs(Scylla paramamosain,BW=17.87±1.49 g)were fed control and high-fat(HF)diets,at both medium salinity(23‰)and low salinity(4‰)for 6 wk,and each treatment had 3 replicates with each replicate containing 10 crabs.The results indicated that a HF diet significantly mitigated the reduction in survival rate,percent weight gain and feed efficiency induced by low salinity(P<0.05).Low salinity lowered lipogenesis and activated lipolysis resulting in lipid depletion in the hepatopancreas of mud crabs(P<0.05).Thus,HF diets enhanced the process of lipolysis to supply more energy.In the gills,low salinity and the HF diet increased the levels of mitochondrial biogenesis markers,the activity of mitochondrial complexes,and the expression levels of genes related to energy metabolism(P<0.05).Consequently,the positive effects of the HF diet on energy metabolism in mud crabs at low salinity promoted osmotic pressure regulation.Specifically,significantly higher haemolymph osmotic pressure and inorganic ion content,as well as higher osmotic pressure regulatory enzyme activity in gills,and gene and protein expression levels of NaK-ATPase were observed in crabs fed the HF diet at low salinity(P<0.05).In summary,high dietary lipid levels improved energy provision to facilitate mitochondrial biogenesis,which increased ATP provision for osmotic pressure regulation of mud crabs.This study also illustrates the importance of dietary lipid nutrition supplementation for low salinity adaptations in mud crabs.
基金supported by National Key R&D Program of China[No.2018YFC0114600]National Natural Science Foundation of China[No.82170547,No.81873558].
文摘Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation.The circadian rhythmcontrols cell proliferation and energy metabolism.However,the role of circadian genes in inflammatory bowel disease is largely unknown.The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism.Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days,whereas those in the control group were not.Subsequently,half of the mice in the control and jet-lagged groups were given dextran sodium sulfate(DSS)to induce colitis.Mice in each group were euthanized at zeitgeber time(ZT)0,ZT4,ZT8,ZT12,ZT16,and ZT20.To investigate the effects of jet lag on the mice,colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes(Bmal1,Clock,Per1,Per2,Cry1,Cry2,and Nr1d1).We analysed the mitochondrial morphology,adenosine triphosphate(ATP)levels,and the expression of dynamin-related protein 1(Drp1)and ser637-phosphorylated(p)-Drp1,which are closely related to ATP production.We further investigated the effect of PER2 knockdown in the colon epithelial cells(CCD 841 CoN)by measuring ATP and cell proliferation levels.Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice,altered the mitochondrial morphology of the colon specimens,decreased the expression of p-Drp1,reduced ATP production,and exacerbated inflammatory responses in mice with DSS-induced colitis.Additionally,silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation.Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis.
