Crocetin protects cardiomyocytes against hypoxia/reoxygenation injury by attenuating Drp1-mediated mitochondrial fission via PGC-1α  

作　　者：You-Ling MOU Rui ZHAO Shi-Ying LYU Zi-Yi ZHANG Mei-Fei ZHU Qian LIU 

机构地区：[1]School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,China [2]Department of Critical Care Medicine,the First Affiliated Hospital,Zhejiang Chinese Medical University,Hangzhou,China

出　　处：《Journal of Geriatric Cardiology》2023年第1期68-82,共15页老年心脏病学杂志（英文版）

基　　金：supported by the grants from National Natural Science Foundation of China(No.81903830);the Natural Science Foundation of Zhejiang Province(No.LY21H280005);the Research Project of Zhejiang Chinese Medical University(No.2021JKZK TS023B);the 2021 Innovation and Entrepreneurship Training Program for College Students(No.S202110344009).

摘　　要：BACKGROUND Saffron(Crocus sativus L.)has been traditionally used as food,spice,and medicine.Crocetin(CRT),as main bioactive component of saffron,has accumulated pieces of beneficial evidence on myocardial ischemia/reperfusion(I/R)injury.However,the mechanisms are poorly explored.This study aims to investigate the effects of CRT on H9c2 cells under hypoxia/reoxygenation(H/R)and elucidated the possible underlying mechanism.METHODS H/R attack was performed on H9c2 cells.Cell counting kit-8 was used to detect the cell viability.Cell samples and culture supernatants were evaluated via commercial kits to measure the superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,and cellular adenosine triphosphate(ATP)content.Various fluorescent probes were used to detect cell apoptosis,intracellular and mitochondrial reactive oxygen species(ROS)content,mitochondrial morphology,mitochondrial membrane potential(MMP),and mitochondrial permeability transition pore(mPTP)opening.Proteins were evaluated via Western Blot.RESULTS H/R exposure severely reduced cell viability and increased LDH leakage.Peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)suppression and dynamin-related protein 1(Drp1)activation were coincided with excessive mitochondrial fission,mitochondrial permeability transition pore(mPTP)opening and mitochondrial membrane potential(MMP)collapse in H9c2 cells treated with H/R.Mitochondria fragmentation under H/R injury induced ROS over-production,oxidative stress,and cell apoptosis.Notably,CRT treatment significantly prevented mitochondrial fission,mPTP opening,MMP loss,and cell apoptosis.Moreover,CRT sufficiently activated PGC-1α and inactivated Drp1.Interestingly,mitochondrial fission inhibition with mdivi-1 similarly suppressed mitochondrial dysfunction,oxidative stress and cell apoptosis.However,silencing PGC-1α with small interfering RNA(siRNA)abolished the beneficial effects of CRT on H9c2 cells under H/R injury,accompanied with increased Drp1 and p-Drp1ser616 levels.Furthermore,over-expr

关 键 词：Drp1 INJURY traditionally 

分 类 号：R285[医药卫生—中药学]