Objective We previously reported that mutations in inner mitochondrial membrane peptidase 2-like(Immp2l)increase infarct volume,enhance superoxide production,and suppress mitochondrial respiration after transient cere...Objective We previously reported that mutations in inner mitochondrial membrane peptidase 2-like(Immp2l)increase infarct volume,enhance superoxide production,and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury.The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice.Methods Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0,1,5,and 24 h of reperfusion.The effects of Immp2l^(+/−)on mitochondrial membrane potential,mitochondrial respiratory complex III activity,caspase-3,and apoptosis-inducing factor(AIF)translocation were examined.Results Immp2l^(+/−)increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice.Immp2l^(+/−)led to mitochondrial damage,mitochondrial membrane potential depolarization,mitochondrial respiratory complex III activity suppression,caspase-3 activation,and AIF nuclear translocation.Conclusion The adverse impact of Immp2l^(+/−)on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential,inhibition of the mitochondrial respiratory complex III,and activation of mitochondria-mediated cell death pathways.These results suggest that patients with stroke carrying Immp2l^(+/−)might have worse and more severe infarcts,followed by a worse prognosis than those without Immp2l mutations.展开更多
AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondri...AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS： Wistar rats were divided into three groups： Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment （2 μg/1O0 g bw/d）. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS： Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential （in status 4 and 3）; an increase of intramitochondrial reactive oxigen species （ROS） generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION： These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.展开更多
OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated ...OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated with polyphyllinⅠ,after which DRP1-dependent mitochondrial fission and apoptosis,mitophagy and PINK1/PARK2 pathway were evaluated.A genetic approach was employed to determine how knockdown of PINK1 with sh RNA regulates polyphyllinⅠ-induced mitophagy and apoptosis.The inhibitory effect of polyphyllinⅠon tumor growth in a breast cancer cell xenograft mouse model was also examined.RESULTS PolyphyllinⅠenhanced the stabilization of full-length PINK1at the mitochondrial surface,leading to PARK2 recruitment to mitochondria,and culminating in mitophagy.PolyphyllinⅠalso induced dephosphorylation of DRP1 at Ser637 and mitochondrial translocation of DRP1,leading to mitochondrial fission and apoptosis.Knockdown of PINK1 evidently suppressed mitophagy stimulated by polyphyllinⅠ,and markedly enhanced DRP1-dependent mitochondrial fission and apoptosis induced by polyphyl inⅠ.Furthermore,suppression of DRP1 by mdivi-1 or sh RNA inhibits PINK1 knockdown-mediated mitochondrial fragmentation and apoptosis in response to polyphyllinⅠtreatment,suggesting that depletion of PINK1 lead to mitochondrial fragmentation due to excessive fission.Our in vivo study also showed that knockdown of PINK1potentiated polyphyllinⅠ-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model.CONCLUSION Our study provides a mechanism to support the role of PINK1 in the regulation of polyphyl inⅠ-induced mitophagy and apoptosis,and suggest polyphylinⅠas a potential drug for treatment of breast cancer.展开更多
[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region（CR） were...[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region（CR） were PCR amplified from the wild R. curvicornis populations from the Liaodong Bay（n=22） and the northern Yellow Sea（n=18）, sequenced and analyzed for genetic diversity. [Result] The contents of A, T, C and G of 624 bp COⅠ gene were 24.09%, 31.04%, 25.28%, and 19.59%, and those of 460 bp CR fragment were 32.96%, 32.80%, 14.86% and 19.38%, respectively. The total number of variable sites, average number of nucleotide differences（ k）, haplotype diversity（H） and nucleotide diversity（π） based on COⅠ gene were 38, 4.67,（0.96±0.02） and（0.007 5±0.004 2）, and those based on CR fragment were 26, 3.35,（0.97 ±0.02） and（0.007 3±0.004 3）, respectively. Based on mitochondrial COⅠ gene and CR, the genetic diversity of Liaodong Bay population was lower than that of the northern Yellow Sea population. The AMOVA analysis based on CR fragments revealed almost significant genetic divergence between the Liaodong Bay and the northern Yellow Sea populations, while there was no significant genetic divergence based on COⅠ gene. The results showed that CR and COⅠ gene are effective molecular markers for detecting the genetic diversity of R. curvicornis population, while CR is more reliable than COⅠ gene in detecting the genetic structure. [Conclusion] CR is an appropriate marker for genetic analysis of marine fish population.展开更多
The protecting effect of histidine on the photodamage of pigments and proteins of the isolated PSⅠ particles from the chloroplast of Spinacia oleracea L. during the strong illumination (2 300 μmol·m -2 ...The protecting effect of histidine on the photodamage of pigments and proteins of the isolated PSⅠ particles from the chloroplast of Spinacia oleracea L. during the strong illumination (2 300 μmol·m -2 ·s -1 ) was studied by spectroscopy and SDS_PAGE. The absorbance of PSⅠ particles decreased during the strong illumination treatment, but the decrease would be slowed down in the presence of externally added histidine after 30 min illumination. The decrease of CD (circular dichroism) signal intensities of PSⅠ particles also was slowed down by the added histidine after about 10 min illumination. The retarded protecting effect of the added histidine on the photobleaching of pigments of PSⅠ complexes implied that the mechanisms of photoinhibition of isolated PSⅠ complexes are different from early stage to later stage during the strong illumination treatment. In addition, the added histidine suppressed the decrease of 77 K fluorescence yield of PSⅠ particles during the illumination. SDS_PAGE showed that the added histidine not only protected the reaction center proteins of PSⅠ particles, but also protected other subunits of PSⅠ particles from degradation.展开更多
Organelle-targeted imaging can provide information on cellular functions and intracellular interactions,being significant for disease diagnosis.The use of room-temperature phosphorescence(RTP)in organelle-targeted ima...Organelle-targeted imaging can provide information on cellular functions and intracellular interactions,being significant for disease diagnosis.The use of room-temperature phosphorescence(RTP)in organelle-targeted imaging can fully utilize its unique characteristics of long wavelength and deep penetration.However,this technology has long been plagued by insufficient probe targeting and limited luminous intensity.In this work,we prepared a series of complexes composed of multicationic persulfurated arenes and biomacromolecules via electrostatic interactions in 1:1 stoichiometry for high-contrast mitochondrial-targeted RTP imaging.Such an electrostatic interaction design effectively prevented the self-aggregation of the probes,which is not conducive to mitochondrial targeting.Simultaneously,it suppressed the non-radiative decay to the maximum extent,enabling the probes to exhibit strong RTP signals both in aqueous solution and at the cellular level.Furthermore,the biomacromolecules can serve as carriers for an electrostatic interaction transfer of the persulfurated arenes to mitochondria.This leads to high mitochondrial targeting Pearson's correlation coefficients of the probes and high-contrast RTP imaging effects,as well as the independence of the co-incubated probe concentration.These results provide new insights for the development of targeted imaging technologies.展开更多
Pathological cardiac hypertrophy,a major contributor to heart failure,is closely linked to mitochondrial function.The roles of long noncoding RNAs(lncRNAs),which regulate mitochondrial function,remain largely unexplor...Pathological cardiac hypertrophy,a major contributor to heart failure,is closely linked to mitochondrial function.The roles of long noncoding RNAs(lncRNAs),which regulate mitochondrial function,remain largely unexplored in this context.Herein,a previously unknown lncRNA,Gm20257,was identified.It markedly increased under hypertrophic stress in vivo and in vitro.The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy.Conversely,the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensinⅡ-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively,thus restoring cardiac function.Importantly,Gm20257 restored mitochondrial complexⅣlevel and enhanced mitochondrial function.Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator–activated receptor coactivator-1(PGC-1α),which could increase mitochondrial complex IV.Subsequently,Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α.Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1αwas a direct downstream target of Gm20257.This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP.These findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complexⅣaxis,offering a novel approach for attenuating pathological cardiac hypertrophy.展开更多
AIM: To investigate mitochondrial factors associated with Leber hereditary optic neuropathy (LHON) through complete sequencing and analysis of the mitochondrial genome of Chinese patients with this disease. METHODS: T...AIM: To investigate mitochondrial factors associated with Leber hereditary optic neuropathy (LHON) through complete sequencing and analysis of the mitochondrial genome of Chinese patients with this disease. METHODS: Two unrelated southern Chinese families with LHON and 10 matched healthy controls were recruited, and their entire mitochondrial DNA (mtDNA) was amplified and sequenced with the universal M13 primer. Then DNA sequence analysis and variation identification were performed by DNAssist and Chromas 2 software and compared with authoritative databases such as Mitomap. RESULTS: Mutational analysis of mtDNA in these two Chinese pedigrees revealed one common LHON-associated mutation, G11778A (Arg -> His), in the MT-ND4 gene. In addition, there were two secondary mutations in Pedigree 1: C34971 (Ala -> Val), and C3571T (Leu -> Phe) in the MT-ND1 gene, which have not been reported; and two secondary mutations occurred in Pedigree 2: A10398G (Thr -> Ala) in the MT-ND3 gene, and T14502C (Ile -> Val) in the MT-ND6 gene. Three polymorphisms, A73G, G94A and A263G in the mtDNA control region, were also found. CONCLUSION: Our study confirmed that the known MT-ND4* G11778A mutation is the most significant cause of LHON. The C3497T and C3571T mutations in Pedigree 1 were also both at hot-spots of MT-ND1; they may affect the respiratory chain in coordination with the primary mutation G11778A. In Pedigree 2, the two secondary mutations A10398G of MT-ND3 and T14502C of MT-ND6 may influence mitochondrial respiratory complex I, leading to the mitochondrial respiratory chain dysfunction which results in optic atrophy together with G11778A. Therefore, not only the common primary LHON mutation is responsible for the visual atrophy, but other secondary mtDNA mutations should also be considered when giving genetic counseling.展开更多
The synthesis,structure and luminescent property of a tetranuclear gold（Ⅰ）complex with doubly bridging diethyldithiocarbamate（Et2dtc）and 1,1-bis（diphenylphosphino）ethene（（Ph2P）2C=CH2）are described.The compl...The synthesis,structure and luminescent property of a tetranuclear gold（Ⅰ）complex with doubly bridging diethyldithiocarbamate（Et2dtc）and 1,1-bis（diphenylphosphino）ethene（（Ph2P）2C=CH2）are described.The complex crystallizes in monoclinic space group C2/c with a=26.785（7）,b=25.654（6）,c=12.277（3）A,β=106.879（5）°,V=8073（4）A^3,Z=8,C31H32Au2F6NO3P2S2Sb,Mr=1222.32,Dc=2.011 g/cm^3,F（000）=4592,Rint=0.0529,T=293（2）K,μ=8.157 mm^（-1）,the final R=0.0464 and wR=0.1444 for 5804 observed reflections with I〉2σ（Ⅰ）.The intramolecular and intermolecular Au¨Au distances are 2.8670（9）and 3.2367（9）A,respectively.Weak emission appears at 517 nm at room temperature in the solid state.展开更多
The six multiimidazole copper（Ⅰ） complexes are utilized to mimic tyrosinase. The main product is 3,5-di-t-butylcatechol from o-hydroxylation of the substrate 2,4-di-t-butylphenol. The highest yield of catechol is u...The six multiimidazole copper（Ⅰ） complexes are utilized to mimic tyrosinase. The main product is 3,5-di-t-butylcatechol from o-hydroxylation of the substrate 2,4-di-t-butylphenol. The highest yield of catechol is up to 82.2% and selectivity 94.8% by [Cu（Ⅰ）2（3b）（MeCN）2]（CIO4）2 and O2 under mild conditions, which are found to be more efficient than that already reported.展开更多
Three polymeric copper（Ⅰ） halide complexes beating phosphine and N-donor bridging ligands, [（PPh3）2Cu2（μ-Br）2（μ-4,4＇-bipy）]∞ 1 （bipy = bipyridine）, [（PPh3）2Cu2（μ-Br）2（μ- bpe）]∞ 2 （bpe = trans-...Three polymeric copper（Ⅰ） halide complexes beating phosphine and N-donor bridging ligands, [（PPh3）2Cu2（μ-Br）2（μ-4,4＇-bipy）]∞ 1 （bipy = bipyridine）, [（PPh3）2Cu2（μ-Br）2（μ- bpe）]∞ 2 （bpe = trans-1,2-bis（4-pyridyl）ethene） and [（PPh3）2Cu2（μ-Cl）2（μ-bpe）]∞ 3, were synthesized by the multilayer diffusion method, and the structures were refined by single-crystal X-ray diffraction. Complex 1 crystallizes in triclinic, space group P1^- with a = 9.122（3）, b = 9.322（3）, c = 13.201（4） A, α = 106.440（4）, β= 105.965（5）, γ= 94.167（5）°, V = 1021.3（6） A^3, Mr= 967.62, Z = 1, De= 1.573 g/cm^3, F（000） = 486, μ = 3.111 mm^-1, the final R = 0.0383 and ωR = 0.0960 for 2792 observed reflections （I 〉 2σ（I））. Complex 2 crystallizes in triclinic, space group P1^- with a = 9.420（3）, b = 10.209（4）, c = 12.407（4） A, α = 104.136（6）, β = 108.132（5）, γ= 95.338（6）°, V = 1081.0（7） A^3, Mr= 496.83, Z = 2, Dc= 1.526 g/cm^3, F（000） = 500, μ = 2.941 mm^-1, the final R = 0.0445 and ωR = 0.1117 for 3251 observed reflections （I 〉 2σ（I））. Complex 3 crystallizes in triclinic, space group P1^- with a = 8.32（1）, b = 11.53（2）, c = 13.94（3） A, α = 109.57（3）, β= 93.85（3）, γ= 97.28（3）°, V= 1242（4） A^3, Mr= 1074.59, Z = 1, Dc = 1.436 g/cm^3, F（000） = 548, μ = 1.279 mm^-1, the final R = 0.0786 and ωR = 0.1586 for 2266 observed reflections （I 〉 2σ（I））. The complexes exhibit intensive solid-state photoluminescence tentatively assigned to an admixture of triplet intraligand （IL） and metal-to-ligand charge-transfer （MLCT） excited state.展开更多
The electronic structure and electronic absorption spectra of binuclear Au(Ⅰ) complexes with bidentate phophines and a bidentate ylid ligand have been studied using quasirelativistic pseudopotential ab initio cal...The electronic structure and electronic absorption spectra of binuclear Au(Ⅰ) complexes with bidentate phophines and a bidentate ylid ligand have been studied using quasirelativistic pseudopotential ab initio calculations at the HF and MP2 levels by the LANL2DZ basis sets. The electronic properties of the spectral transition and Au(Ⅰ)—Au(Ⅰ) interaction were also discussed.展开更多
A novel mixed-valence copper (Ⅰ,Ⅱ) complex Cu3 [CH2=C(CH3) COO]5 (imH)3 (H2O)has been synthesized and characterized by XPS spectra and single crystal X-ray structural analysis.The title complex crystallized in monoc...A novel mixed-valence copper (Ⅰ,Ⅱ) complex Cu3 [CH2=C(CH3) COO]5 (imH)3 (H2O)has been synthesized and characterized by XPS spectra and single crystal X-ray structural analysis.The title complex crystallized in monoclinic space group P21/c, with α=11 .225 (3), b=13.9023 (12),c=24.559 (2), β=92.372 (10)°and Z=4. Final R=0.0495 for 5546 reflections [I＞2σ (Ⅰ)].展开更多
The vinylidenebis（diphenylphosphine） （vdpp） reacts with CuBr to give a tetranuclear complex, [Cu4（μ3-Br）2（μ2-Br）2（μ2-vdpp）2（CH3CN）2]·（CH3CN）2 1. The title complex has crystallo- graphically impos...The vinylidenebis（diphenylphosphine） （vdpp） reacts with CuBr to give a tetranuclear complex, [Cu4（μ3-Br）2（μ2-Br）2（μ2-vdpp）2（CH3CN）2]·（CH3CN）2 1. The title complex has crystallo- graphically imposed centrosymmetry and presents a CuaBr4 core with distorted stair-like structure. All copper（I） atoms in 1 assume distorted tetrahedral coordination geometry. The distance of 2.7745（11） A between the two copper centers indicates the presence of ligand-supported Cu…Cu interactions. Crystal data for 1： C_60H_56Br_4Cu_4N_4P_4, Mr= 1530.77, triclinic, space group P1, a = 11.6593（9）, b = 11.7181（9）, c = 13.8711（11） А, a = 110.1020（10）, β = 102.0050（10）, γ = 109.8040（10）°, V = 1557.5（2） А^3, Z = 1, Dc = 1.632 g/cm^3, F（000） = 760, λ= 0.71073А, T = 298（2） K, 2θmax = 50.04°,μ= 4.056 mm^-1, S = 1.181, R = 0.0507 and wR = 0.1025.展开更多
The complex [Cu (dppp)2] (ClO4) was prepared by the reaction ofcopper (Ⅱ) perchlorate wlth bis(diphenylphosphino) propane (dppp) in methanol, andits crystal structure was determlned by X-ray crystallography. The crys...The complex [Cu (dppp)2] (ClO4) was prepared by the reaction ofcopper (Ⅱ) perchlorate wlth bis(diphenylphosphino) propane (dppp) in methanol, andits crystal structure was determlned by X-ray crystallography. The crystal is monoclin-ic, space group P1, M. = 1019. 90 with cell parameters a = 11. 951 (6), b = 12. 178(4), c=18. 413(5) A, α=70. 52(3), β=83. 56(4), γ=77. 61 (4), V=2465. 2 A3,Z = 2, Dc = 1. 371 g/cm3. The structure was solved by direct methods and refined byblock-diagonal and full-matrix least-squares methods to a final R of 0. 043 for 4085 in-dependent reflections of I>3σ(I). In this complex [Cu (dppp)2] (ClO4), dppp func-tions as a bidentate chelate ligand. The four P atoms from two dppp are coordinated tothe tetrahedral copper (P4).展开更多
A tetranuclear copper (I) complex of the ditholate ligand fused with a TTF moiety hasbeen synthesized and characterized crystallographically. This is the first example of a metaJ clustercoordinated with the new type l...A tetranuclear copper (I) complex of the ditholate ligand fused with a TTF moiety hasbeen synthesized and characterized crystallographically. This is the first example of a metaJ clustercoordinated with the new type ligand. The complex shows interesting redox and radical properties.展开更多
Four novel Cu（Ⅰ） complexes,[Cu（o-PYO）（PPh3）2]BF4（1）,[Cu（o-PYO）（DPEphos）]BF4（2）,[Cu2 （o-PYO）（PPh3）3（CH3CN）]（BF4）2（3） and [Cu2（o-PYO）（DPEphos）2 ]（BF4）2（4） （o-PYO=2,5bis（pyridyl）-1,3,4...Four novel Cu（Ⅰ） complexes,[Cu（o-PYO）（PPh3）2]BF4（1）,[Cu（o-PYO）（DPEphos）]BF4（2）,[Cu2 （o-PYO）（PPh3）3（CH3CN）]（BF4）2（3） and [Cu2（o-PYO）（DPEphos）2 ]（BF4）2（4） （o-PYO=2,5bis（pyridyl）-1,3,4-oxadiazole,PPh 3=triphenylphosphine,DPEphos=bis（2-（diphenylphosphanyl）phenyl）ether）,have been synthesized and characterized by 1 H NMR,elemental analysis and single-crystal X-ray diffraction.The central cuprous ions in all complexes are surrounded by N and P atoms to form a distorted tetrahedral geometry,although one of the cuprous ions in complex 3 is coordinated by a PPh3 and an acetonitrile molecule due to the steric hindrance and weak coordination ability from monodentate PPh3 ligand.The UV-vis absorption spectra in CH2Cl2 show the characteristic metal-to-ligand charge transfer （MLCT） absorption bands in the region of 360-480nm.Four Cu（I） complexes exhibit yellow to orange-red phosphorescence with the emission maximum at 572,577,562 and 597nm,respectively in the solid state.展开更多
基金This study was supported by the National Natural Science Foundation of China(Nos.81360196,81760240the Natural Science Foundation of Ningxia(No.2022AAC03159)the Ningxia Innovation Team of the Foundation and Clinical Research of Diabetes and Its Complications(No.NXKJT2019010).
文摘Objective We previously reported that mutations in inner mitochondrial membrane peptidase 2-like(Immp2l)increase infarct volume,enhance superoxide production,and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury.The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice.Methods Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0,1,5,and 24 h of reperfusion.The effects of Immp2l^(+/−)on mitochondrial membrane potential,mitochondrial respiratory complex III activity,caspase-3,and apoptosis-inducing factor(AIF)translocation were examined.Results Immp2l^(+/−)increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice.Immp2l^(+/−)led to mitochondrial damage,mitochondrial membrane potential depolarization,mitochondrial respiratory complex III activity suppression,caspase-3 activation,and AIF nuclear translocation.Conclusion The adverse impact of Immp2l^(+/−)on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential,inhibition of the mitochondrial respiratory complex III,and activation of mitochondria-mediated cell death pathways.These results suggest that patients with stroke carrying Immp2l^(+/−)might have worse and more severe infarcts,followed by a worse prognosis than those without Immp2l mutations.
基金Supported by The Spanish Program I + D, SAF 2005/08113
文摘AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS： Wistar rats were divided into three groups： Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment （2 μg/1O0 g bw/d）. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three expedmental groups. RESULTS： Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential （in status 4 and 3）; an increase of intramitochondrial reactive oxigen species （ROS） generation and a significant reduction of ATPase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION： These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.
基金The project supported by National Natural Science Foundation of China(81402970,81402202,81402013,81202869)
文摘OBJECTIVE To elucidate the molecular mechanism and the anti-breast cancer effect of polyphyllinⅠ,which is a natural compound extracted from Rhizoma of Paris polyphyllin.METHODS Human breast cancer cells were treated with polyphyllinⅠ,after which DRP1-dependent mitochondrial fission and apoptosis,mitophagy and PINK1/PARK2 pathway were evaluated.A genetic approach was employed to determine how knockdown of PINK1 with sh RNA regulates polyphyllinⅠ-induced mitophagy and apoptosis.The inhibitory effect of polyphyllinⅠon tumor growth in a breast cancer cell xenograft mouse model was also examined.RESULTS PolyphyllinⅠenhanced the stabilization of full-length PINK1at the mitochondrial surface,leading to PARK2 recruitment to mitochondria,and culminating in mitophagy.PolyphyllinⅠalso induced dephosphorylation of DRP1 at Ser637 and mitochondrial translocation of DRP1,leading to mitochondrial fission and apoptosis.Knockdown of PINK1 evidently suppressed mitophagy stimulated by polyphyllinⅠ,and markedly enhanced DRP1-dependent mitochondrial fission and apoptosis induced by polyphyl inⅠ.Furthermore,suppression of DRP1 by mdivi-1 or sh RNA inhibits PINK1 knockdown-mediated mitochondrial fragmentation and apoptosis in response to polyphyllinⅠtreatment,suggesting that depletion of PINK1 lead to mitochondrial fragmentation due to excessive fission.Our in vivo study also showed that knockdown of PINK1potentiated polyphyllinⅠ-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model.CONCLUSION Our study provides a mechanism to support the role of PINK1 in the regulation of polyphyl inⅠ-induced mitophagy and apoptosis,and suggest polyphylinⅠas a potential drug for treatment of breast cancer.
基金Supported by the National Key R&D Program of China(2017YFC1404400)The National Natural Science Foundation of China(31770458)
文摘[Object] This study was conducted to explore the genetic diversity and structure of the wild Repomucenus curvicornis inhabiting Liaoning Coast, China. [Method] The mitochondrial COⅠ gene and control region（CR） were PCR amplified from the wild R. curvicornis populations from the Liaodong Bay（n=22） and the northern Yellow Sea（n=18）, sequenced and analyzed for genetic diversity. [Result] The contents of A, T, C and G of 624 bp COⅠ gene were 24.09%, 31.04%, 25.28%, and 19.59%, and those of 460 bp CR fragment were 32.96%, 32.80%, 14.86% and 19.38%, respectively. The total number of variable sites, average number of nucleotide differences（ k）, haplotype diversity（H） and nucleotide diversity（π） based on COⅠ gene were 38, 4.67,（0.96±0.02） and（0.007 5±0.004 2）, and those based on CR fragment were 26, 3.35,（0.97 ±0.02） and（0.007 3±0.004 3）, respectively. Based on mitochondrial COⅠ gene and CR, the genetic diversity of Liaodong Bay population was lower than that of the northern Yellow Sea population. The AMOVA analysis based on CR fragments revealed almost significant genetic divergence between the Liaodong Bay and the northern Yellow Sea populations, while there was no significant genetic divergence based on COⅠ gene. The results showed that CR and COⅠ gene are effective molecular markers for detecting the genetic diversity of R. curvicornis population, while CR is more reliable than COⅠ gene in detecting the genetic structure. [Conclusion] CR is an appropriate marker for genetic analysis of marine fish population.
文摘The protecting effect of histidine on the photodamage of pigments and proteins of the isolated PSⅠ particles from the chloroplast of Spinacia oleracea L. during the strong illumination (2 300 μmol·m -2 ·s -1 ) was studied by spectroscopy and SDS_PAGE. The absorbance of PSⅠ particles decreased during the strong illumination treatment, but the decrease would be slowed down in the presence of externally added histidine after 30 min illumination. The decrease of CD (circular dichroism) signal intensities of PSⅠ particles also was slowed down by the added histidine after about 10 min illumination. The retarded protecting effect of the added histidine on the photobleaching of pigments of PSⅠ complexes implied that the mechanisms of photoinhibition of isolated PSⅠ complexes are different from early stage to later stage during the strong illumination treatment. In addition, the added histidine suppressed the decrease of 77 K fluorescence yield of PSⅠ particles during the illumination. SDS_PAGE showed that the added histidine not only protected the reaction center proteins of PSⅠ particles, but also protected other subunits of PSⅠ particles from degradation.
基金supported by the National Natural Science Foundation of China(22275038)partially funded by the Swedish Research Council(2022-06725)+1 种基金the support from the Swedish Research Council(2020-04600)funded by the European Union(ERC,LUMOR,101077649)the support from the Swedish Science Research Council(2022-03405)。
文摘Organelle-targeted imaging can provide information on cellular functions and intracellular interactions,being significant for disease diagnosis.The use of room-temperature phosphorescence(RTP)in organelle-targeted imaging can fully utilize its unique characteristics of long wavelength and deep penetration.However,this technology has long been plagued by insufficient probe targeting and limited luminous intensity.In this work,we prepared a series of complexes composed of multicationic persulfurated arenes and biomacromolecules via electrostatic interactions in 1:1 stoichiometry for high-contrast mitochondrial-targeted RTP imaging.Such an electrostatic interaction design effectively prevented the self-aggregation of the probes,which is not conducive to mitochondrial targeting.Simultaneously,it suppressed the non-radiative decay to the maximum extent,enabling the probes to exhibit strong RTP signals both in aqueous solution and at the cellular level.Furthermore,the biomacromolecules can serve as carriers for an electrostatic interaction transfer of the persulfurated arenes to mitochondria.This leads to high mitochondrial targeting Pearson's correlation coefficients of the probes and high-contrast RTP imaging effects,as well as the independence of the co-incubated probe concentration.These results provide new insights for the development of targeted imaging technologies.
基金supported by the National Natural Science Foundation of China(Nos.82170299 and 82003757)Major Projects of the National Natural Science Foundation of China(No.82330011)+1 种基金the National Natural Science Foundation of China(No.82370279)the Postdoctoral Starting Fund of Heilongjiang Province(No.LBH-Q21121).
文摘Pathological cardiac hypertrophy,a major contributor to heart failure,is closely linked to mitochondrial function.The roles of long noncoding RNAs(lncRNAs),which regulate mitochondrial function,remain largely unexplored in this context.Herein,a previously unknown lncRNA,Gm20257,was identified.It markedly increased under hypertrophic stress in vivo and in vitro.The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy.Conversely,the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensinⅡ-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively,thus restoring cardiac function.Importantly,Gm20257 restored mitochondrial complexⅣlevel and enhanced mitochondrial function.Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator–activated receptor coactivator-1(PGC-1α),which could increase mitochondrial complex IV.Subsequently,Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α.Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1αwas a direct downstream target of Gm20257.This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP.These findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complexⅣaxis,offering a novel approach for attenuating pathological cardiac hypertrophy.
基金Supported by the National Natural Science Foundation of China(No.J0710043)
文摘AIM: To investigate mitochondrial factors associated with Leber hereditary optic neuropathy (LHON) through complete sequencing and analysis of the mitochondrial genome of Chinese patients with this disease. METHODS: Two unrelated southern Chinese families with LHON and 10 matched healthy controls were recruited, and their entire mitochondrial DNA (mtDNA) was amplified and sequenced with the universal M13 primer. Then DNA sequence analysis and variation identification were performed by DNAssist and Chromas 2 software and compared with authoritative databases such as Mitomap. RESULTS: Mutational analysis of mtDNA in these two Chinese pedigrees revealed one common LHON-associated mutation, G11778A (Arg -> His), in the MT-ND4 gene. In addition, there were two secondary mutations in Pedigree 1: C34971 (Ala -> Val), and C3571T (Leu -> Phe) in the MT-ND1 gene, which have not been reported; and two secondary mutations occurred in Pedigree 2: A10398G (Thr -> Ala) in the MT-ND3 gene, and T14502C (Ile -> Val) in the MT-ND6 gene. Three polymorphisms, A73G, G94A and A263G in the mtDNA control region, were also found. CONCLUSION: Our study confirmed that the known MT-ND4* G11778A mutation is the most significant cause of LHON. The C3497T and C3571T mutations in Pedigree 1 were also both at hot-spots of MT-ND1; they may affect the respiratory chain in coordination with the primary mutation G11778A. In Pedigree 2, the two secondary mutations A10398G of MT-ND3 and T14502C of MT-ND6 may influence mitochondrial respiratory complex I, leading to the mitochondrial respiratory chain dysfunction which results in optic atrophy together with G11778A. Therefore, not only the common primary LHON mutation is responsible for the visual atrophy, but other secondary mtDNA mutations should also be considered when giving genetic counseling.
基金financial supports from the NNSFC(20931006,U0934003,and 91122006)the NSF of Fujian Province(2011J01065)
文摘The synthesis,structure and luminescent property of a tetranuclear gold（Ⅰ）complex with doubly bridging diethyldithiocarbamate（Et2dtc）and 1,1-bis（diphenylphosphino）ethene（（Ph2P）2C=CH2）are described.The complex crystallizes in monoclinic space group C2/c with a=26.785（7）,b=25.654（6）,c=12.277（3）A,β=106.879（5）°,V=8073（4）A^3,Z=8,C31H32Au2F6NO3P2S2Sb,Mr=1222.32,Dc=2.011 g/cm^3,F（000）=4592,Rint=0.0529,T=293（2）K,μ=8.157 mm^（-1）,the final R=0.0464 and wR=0.1444 for 5804 observed reflections with I〉2σ（Ⅰ）.The intramolecular and intermolecular Au¨Au distances are 2.8670（9）and 3.2367（9）A,respectively.Weak emission appears at 517 nm at room temperature in the solid state.
基金the support from the National Natural Science Foundation of China(No.20172038).
文摘The six multiimidazole copper（Ⅰ） complexes are utilized to mimic tyrosinase. The main product is 3,5-di-t-butylcatechol from o-hydroxylation of the substrate 2,4-di-t-butylphenol. The highest yield of catechol is up to 82.2% and selectivity 94.8% by [Cu（Ⅰ）2（3b）（MeCN）2]（CIO4）2 and O2 under mild conditions, which are found to be more efficient than that already reported.
基金the State Key Project (No. 2005CCA06800)the NSFC/RGC Joint Research Foundation (50418010)
文摘Three polymeric copper（Ⅰ） halide complexes beating phosphine and N-donor bridging ligands, [（PPh3）2Cu2（μ-Br）2（μ-4,4＇-bipy）]∞ 1 （bipy = bipyridine）, [（PPh3）2Cu2（μ-Br）2（μ- bpe）]∞ 2 （bpe = trans-1,2-bis（4-pyridyl）ethene） and [（PPh3）2Cu2（μ-Cl）2（μ-bpe）]∞ 3, were synthesized by the multilayer diffusion method, and the structures were refined by single-crystal X-ray diffraction. Complex 1 crystallizes in triclinic, space group P1^- with a = 9.122（3）, b = 9.322（3）, c = 13.201（4） A, α = 106.440（4）, β= 105.965（5）, γ= 94.167（5）°, V = 1021.3（6） A^3, Mr= 967.62, Z = 1, De= 1.573 g/cm^3, F（000） = 486, μ = 3.111 mm^-1, the final R = 0.0383 and ωR = 0.0960 for 2792 observed reflections （I 〉 2σ（I））. Complex 2 crystallizes in triclinic, space group P1^- with a = 9.420（3）, b = 10.209（4）, c = 12.407（4） A, α = 104.136（6）, β = 108.132（5）, γ= 95.338（6）°, V = 1081.0（7） A^3, Mr= 496.83, Z = 2, Dc= 1.526 g/cm^3, F（000） = 500, μ = 2.941 mm^-1, the final R = 0.0445 and ωR = 0.1117 for 3251 observed reflections （I 〉 2σ（I））. Complex 3 crystallizes in triclinic, space group P1^- with a = 8.32（1）, b = 11.53（2）, c = 13.94（3） A, α = 109.57（3）, β= 93.85（3）, γ= 97.28（3）°, V= 1242（4） A^3, Mr= 1074.59, Z = 1, Dc = 1.436 g/cm^3, F（000） = 548, μ = 1.279 mm^-1, the final R = 0.0786 and ωR = 0.1586 for 2266 observed reflections （I 〉 2σ（I））. The complexes exhibit intensive solid-state photoluminescence tentatively assigned to an admixture of triplet intraligand （IL） and metal-to-ligand charge-transfer （MLCT） excited state.
文摘The electronic structure and electronic absorption spectra of binuclear Au(Ⅰ) complexes with bidentate phophines and a bidentate ylid ligand have been studied using quasirelativistic pseudopotential ab initio calculations at the HF and MP2 levels by the LANL2DZ basis sets. The electronic properties of the spectral transition and Au(Ⅰ)—Au(Ⅰ) interaction were also discussed.
文摘A novel mixed-valence copper (Ⅰ,Ⅱ) complex Cu3 [CH2=C(CH3) COO]5 (imH)3 (H2O)has been synthesized and characterized by XPS spectra and single crystal X-ray structural analysis.The title complex crystallized in monoclinic space group P21/c, with α=11 .225 (3), b=13.9023 (12),c=24.559 (2), β=92.372 (10)°and Z=4. Final R=0.0495 for 5546 reflections [I＞2σ (Ⅰ)].
基金Supported by the Open Foundation of Ningbo Municipal Key Laboratory (2007A22003)the National Natural Science Foundation of China (20701022)the Ningbo Municipal Natural Science Foundation (2007A610024)
文摘The vinylidenebis（diphenylphosphine） （vdpp） reacts with CuBr to give a tetranuclear complex, [Cu4（μ3-Br）2（μ2-Br）2（μ2-vdpp）2（CH3CN）2]·（CH3CN）2 1. The title complex has crystallo- graphically imposed centrosymmetry and presents a CuaBr4 core with distorted stair-like structure. All copper（I） atoms in 1 assume distorted tetrahedral coordination geometry. The distance of 2.7745（11） A between the two copper centers indicates the presence of ligand-supported Cu…Cu interactions. Crystal data for 1： C_60H_56Br_4Cu_4N_4P_4, Mr= 1530.77, triclinic, space group P1, a = 11.6593（9）, b = 11.7181（9）, c = 13.8711（11） А, a = 110.1020（10）, β = 102.0050（10）, γ = 109.8040（10）°, V = 1557.5（2） А^3, Z = 1, Dc = 1.632 g/cm^3, F（000） = 760, λ= 0.71073А, T = 298（2） K, 2θmax = 50.04°,μ= 4.056 mm^-1, S = 1.181, R = 0.0507 and wR = 0.1025.
文摘The complex [Cu (dppp)2] (ClO4) was prepared by the reaction ofcopper (Ⅱ) perchlorate wlth bis(diphenylphosphino) propane (dppp) in methanol, andits crystal structure was determlned by X-ray crystallography. The crystal is monoclin-ic, space group P1, M. = 1019. 90 with cell parameters a = 11. 951 (6), b = 12. 178(4), c=18. 413(5) A, α=70. 52(3), β=83. 56(4), γ=77. 61 (4), V=2465. 2 A3,Z = 2, Dc = 1. 371 g/cm3. The structure was solved by direct methods and refined byblock-diagonal and full-matrix least-squares methods to a final R of 0. 043 for 4085 in-dependent reflections of I>3σ(I). In this complex [Cu (dppp)2] (ClO4), dppp func-tions as a bidentate chelate ligand. The four P atoms from two dppp are coordinated tothe tetrahedral copper (P4).
文摘A tetranuclear copper (I) complex of the ditholate ligand fused with a TTF moiety hasbeen synthesized and characterized crystallographically. This is the first example of a metaJ clustercoordinated with the new type ligand. The complex shows interesting redox and radical properties.
基金supported by the National Natural Science Foundation of China (Nos. 20874098,51073152 and 50772113)the Natural Science Foundation of Fujian Province (No. 2007F3116)
文摘Four novel Cu（Ⅰ） complexes,[Cu（o-PYO）（PPh3）2]BF4（1）,[Cu（o-PYO）（DPEphos）]BF4（2）,[Cu2 （o-PYO）（PPh3）3（CH3CN）]（BF4）2（3） and [Cu2（o-PYO）（DPEphos）2 ]（BF4）2（4） （o-PYO=2,5bis（pyridyl）-1,3,4-oxadiazole,PPh 3=triphenylphosphine,DPEphos=bis（2-（diphenylphosphanyl）phenyl）ether）,have been synthesized and characterized by 1 H NMR,elemental analysis and single-crystal X-ray diffraction.The central cuprous ions in all complexes are surrounded by N and P atoms to form a distorted tetrahedral geometry,although one of the cuprous ions in complex 3 is coordinated by a PPh3 and an acetonitrile molecule due to the steric hindrance and weak coordination ability from monodentate PPh3 ligand.The UV-vis absorption spectra in CH2Cl2 show the characteristic metal-to-ligand charge transfer （MLCT） absorption bands in the region of 360-480nm.Four Cu（I） complexes exhibit yellow to orange-red phosphorescence with the emission maximum at 572,577,562 and 597nm,respectively in the solid state.
