Dietary l-methionine restriction decreases oxidative stress in porcine liver mitochondria
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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.
author list (cited authors)
Ying, Y., Yun, J. i., Guoyao, W. u., Kaiji, S., Zhaolai, D., & Zhenlong, W. u.