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Protective effect of resveratrol on rat cardiomyocyte H9C2 cells injured by hypoxia/reoxygenation by regulating mitochondrial autophagy via PTEN-induced putative kinase protein 1/Parkinson disease protein 2 signaling pathway     被引量:3

文献类型:期刊文献

中文题名:Protective effect of resveratrol on rat cardiomyocyte H9C2 cells injured by hypoxia/reoxygenation by regulating mitochondrial autophagy via PTEN-induced putative kinase protein 1/Parkinson disease protein 2 signaling pathway

作者:ZHAO Lixia[1,2,3];SUN Wei[4];BAI Decheng[1]

第一作者:赵丽霞;ZHAO Lixia

通信作者:Bai, DC[1]

机构:[1]Institute of Integrated Traditional Chinese and Western Medicine,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China;[2]School of Nursing,Gansu University of Chinese Medicine,Lanzhou 730000,China;[3]Key Laboratory of Dunhuang Medicine,Ministry of Education,Gansu University of Chinese Medicine,Lanzhou 730000,China;[4]Cardiac Surgery,the First Hospital of Lanzhou University,Lanzhou,Gansu 730000,China

第一机构:Institute of Integrated Traditional Chinese and Western Medicine,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China

通信机构:[1]corresponding author), Lanzhou Univ, Lanzhou 730000, Gansu, Peoples R China.

年份:2022

卷号:42

期号:2

起止页码:176

中文期刊名:Journal of Traditional Chinese Medicine

外文期刊名:中医杂志(英文版)

收录:Scopus;CSCD:【CSCD2021_2022】;PubMed;

基金:Supported by the Open Fund of Key Laboratory of Dunhuang Medicine, Ministry of Education (DHYX20-09) and the Youth Research Foundation of the Gansu University of Chinese Medicine (No. ZQ2017-14)

语种:英文

中文关键词:resveratrol;myocytes;cardiac;hypoxia;PTEN phosphohydrolase;Parkinson disease associated proteins;mitochondrial autophagy

摘要:OBJECTIVE:To investigate the protective effect of resveratrol on cardiomyocytes after hypoxia/reoxygenation intervention based on PTEN-induced putative kinase protein 1/Parkinson disease protein 2(PINK1/PARKIN)signaling pathway.METHODS:3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect the effect of resveratrol on the viability of H9C2 cells;the hypoxia/reoxygenation(H/R)model was established in tri-gas incubator;2’,7’-Dichlorofluorescin diacetate staining was used to measure the content of reactive oxygen species(ROS);the changes of mitochondrial membrane potential was determined by 5,5’,6,6’-Tetrachloro-1,1’,3,3’-tetraethyl-imidacarbocyanine iodide staining;the changes of mitochondrial respiratory chain complex activity was evaluated by enzyme activity kits;flow cytometry was used to detect the ratio of apoptotic cells;transmission electron microscope was used to observe the ultrastructure of H9C2 cells;Western blot was used to detect the protein changes of mitochondrial 20 k Da outer membrane protein(TOM20),translocase of inner mitochondrial membrane 23(TIM23),presenilins associated rhomboid-like protein(PARL),PINK1,PARKIN and mitofusin 1(Mfn1),mitofusin 2(Mfn2),phosphotyrosine independent ligand for the Lck SH2 domain of 62 k Da(P62),microtubule-associated protein 1 light chain 3 beta(LC3B);the m RNA levels of PINK1 and PARKIN was detected by quantitative polymerase chain reaction;immunoprecipitation assay was used to detect the interaction between PARKIN and Ubiquitin.RESULTS:Resveratrol could inhibit the proliferation of H9C2 cells in a time-and concentration-dependent manner;however,pretreatment with low cytotoxic resveratrol could reduce the H/R-induced increase in cellular ROS levels,alleviate the loss of mitochondrial membrane potential induced by H/R,inhibit H/R-induced apoptosis of H9C2 cells,and protect the mitochondrial structure and respiratory chain of H9C2 cells from H/R damage.Resveratrol could further increase the levels of p62,PINK1,PARKIN protein,the expression of PINK1,PARKIN m RNA and the ratio of LC3BⅡ/LC3BⅠin H/Rinduced H9C2 cells,inhibit the interaction between PARKIN and Ubiquitin in H/R-induced H9C2 cells,and further reduce the expression of TOM20,TIM23,PARL,Mfn1 and Mfn2 protein in H/R-induced H9C2 cells.The effect of resveratrol is consistent with that of autophagy activator on H/R-induced H9C2 cells.CONCLUSIONS:Resveratrol can protect H9C2 cells from H/R injury,which may be related to resveratrol promoting mitochondrial autophagy by activating PINK1/PARKIN signaling pathway.

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