식이제한이 마우스 신장의 글루타치온 대사과정에 미치는 영향

Effect of Diet Restriction on Renal Glutathione Metabolism in Mice

Various benefits for the maintenance of metabolic homeostasis can be obtained through dietary restriction. Short-term fasting of mice may induce systemic metabolic remodeling, which may have a significant effect on the level of endogenous metabolites. This study was conducted to examine metabolic changes of sulfur-containing substances in the kidneys of fasted mice over 48 h. No change in the concentration of renal methionine was observed over 48 h; however, significant decreases in the concentrations of S-adenosylmethionine and S-adenosylhomocysteine were observed at both 24 and 48 h after fasting. A significant decrease in the concentration of renal cysteine was observed from 24 h, and this was maintained at 48 h. A significant decrease in the concentration of glutathione (GSH) was observed in the kidney at 48 h, whereas increased concentrations of taurine were observed 48 h after fasting. Although significantly increased expression levels of BHMT were observed, markedly decreased expression levels of CβS were observed at 48 h after fasting, indicating activated generation of methionine, but downregulation of cysteine synthesis. The expression level of γ-GCL was not altered by fasting for 48 h; however, a significant increase of cysteine sulfinate decarboxylase mediating the taurine synthesis was observed. Significantly decreased protein expression levels of solute carrier family 7 member 11, which imports extracellular cystine, were observed at 48 h. These results suggest that the renal methionine concentration was maintained during short-term fasting through an increase in the re-methylation of homocysteine. Moreover, a reduction in the concentration of cysteine was the result of an increase in the synthesis of taurine and a decrease in the uptake of extracellular cystine, which may result in a decreased concentration of renal GSH.