title: Dietary L-methionine restriction decreases oxidative stress in porcine liver mitochondria.
abstract: Dietary methionine restriction (MetR) has been reported to improve hepatocyte function in mammals. However, the underlying mechanisms remain largely unknown. This study was conducted with a swine model to test the hypothesis that MetR decreases generation of reactive oxygen species (ROS) and attenuates oxidative damage in hepatic mitochondria. Twenty-four 35-day old pigs were fed a control diet or a Met-restricted diet for two weeks. Liver mitochondria were isolated to determine: 8-oxodG in mitochondrial DNA, oxidative-derived proteins markers, including glutamic semialdehyde (GSA), aminoadipic semialdehydes (AASA), carboxyethyl-lysine (CEL), carboxymethyl-lysine (CML), and malondialdehyde lysine (MDAL), mitochondrial H2O2 generation rate; rates of oxygen consumption; free radical leak (FRL); anti-oxidative capacity, electron transport complex activity; and protein abundances of respiratory chain complex subunits (NDUFA9, SDHA, Core 2, and Cox 1), manganese superoxide dismutase (MnSOD), and apoptosis-inducing factor (AIF). Compared with the control, MetR decreased mitochondrial 8-oxodG content, H2O2 generation, FRL (P<0.05), and increased rates of oxygen consumption. Abundances of markers for protein oxidative damage, including GSA, AASA, CEL, and CML, were decreased (P<0.05) by 40%, 30%, 32%, and 28%, respectively, compared with the control. Western blot analysis revealed that MetR decreased (P<0.05) the protein abundances of complex subunits, NDUFA9 and AIF without affecting expression of SDHA, Core 2, Cox 1 or MnSOD. The complex I activity (P<0.05) were lowered in MetR group as compared with that of control. Collectively, our findings indicate that dietary MetR decreases mitochondrial ROS generation primarily via inhibiting complex I activity and ROS generation rather than augmenting anti-oxidative capacity, thereby ameliorating oxidative damage to hepatic mitochondrial DNA and proteins.
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ying
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Guoyao
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Kaiji
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhaolai
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China. Electronic address: bio2046@hotmail.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhenlong
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D004032:Diet / Q000379:methods; D004579:Electron Transport / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
chemical_list: D005971:Glutamates; D017382:Reactive Oxygen Species; C048496:N(6)-carboxymethyllysine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008715:Methionine; D003849:Deoxyguanosine; D008239:Lysine
keywords: Liver; Methionine restriction; Mitochondrial ROS generation; Oxidative damage