title: Protection of L-methionine against H₂O₂-induced oxidative damage in mitochondria.
abstract: Reactive oxygen species (ROS) is reported to be a critical pathogenic factor and mitochondria is one of the susceptible subcellular organs for oxidative damage. Methionine sulfoxide reductase A (MsrA) is a key anti-oxidant enzyme associated with cytoprotection and previous reports have revealed its importance in mitochondrial function. The anti-oxidation of MsrA is due to Met-centered redox cycle, suggesting that Met-centered redox cycle may play a critical role in mitochondrial protection. L-Methionine (L-Met), a natural amino acid with anti-oxidation activity, can mimic the effect of Met-centered redox cycle. Here, we investigated the protection of L-Met on H(2)O(2)-induced oxidative damage in mitochondria. Our study demonstrated that L-Met protected H(2)O(2)-induced injury in CHO cells. Cytoprotections of L-Met at low concentrations (1-5mM) were abolished by dimethyl sulfoxide (DMSO), a competitive inhibitor of MsrA function, suggesting that these effects may involve the participation of MsrA. Overexpression of MsrA in CHO cells protected mitochondria from H(2)O(2)-induced downtrend of membrane potential and production of mitochondrial superoxide. Pre-treatment with L-Met (1mM) produced a similar effect on the mitochondrial protection against H(2)O(2). Furthermore, it was observed that topical application of L-Met can prevent 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced oxidative damage in the skin of mice. These results suggest that anti-oxidation activity of L-Met may promise a new strategy for the prevention of oxidative stress-induced damage.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Long
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zeng
authors.forename: Xin-Lei
authors.initials: XL
authors.lastname: Guan
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: You
authors.initials: Y
authors.lastname: Jin
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Xie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008564:Membrane Potentials; D008715:Methionine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008715:Methionine; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate