S-methyl-L-cysteine Protects against Antimycin A-induced Mitochondrial Dysfunction in Neural Cells via Mimicking Endogenous Methionine-centered Redox Cycle  

作　　者：Lan NI Xin-lei GUAN Fu-feng CHEN Peng-fei WU 

机构地区：[1]Department of Pharmacology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Department of Pharmacy,Wuhan Puai Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430033,China [3]Tongji-Rongcheng Center for Biomedicine,Wuhan 430030,China [4]Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province,Wuhan 430030,China

出　　处：《Current Medical Science》2020年第3期422-433,共12页当代医学科学（英文）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.81773712,No.81473198);the Foundation for Innovative Research Groups of NSFC(No.81721005);the National Basic Research Program of China(973 Program,No.2014CB744601);Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province(No.2015CFA020);PCSIRT(No.IRT13016).

摘　　要：Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration.Mitochondria-targeted antioxidants,such as MitoQ,have emerged as potentially effective antioxidant therapies.Methionine sulfoxide reductase A(MsrA)is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine(Met)-centered redox cycle(MCRC).In this study,we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells.This antioxidation was largely dependent on the Met oxidase activity of MsrA.S-methyl-L-cysteine(SMLC),a natural analogue of Met that is abundantly found in garlic and cabbage,could activate the Met oxidase activity of MsrA to scavenge free radicals.Furthermore,SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium(MPP+)-induced neurotoxicity.Thus,our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.

关 键 词：methionine sulfoxide reductase A Met oxidase S-methyl-L-cysteine NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM 

分 类 号：G23[文化科学]