In this study, treatment of C57BL/6J （wild type, WT） mice fed a high-fat diet （HFD） with retinoic acid （RA） decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis,...In this study, treatment of C57BL/6J （wild type, WT） mice fed a high-fat diet （HFD） with retinoic acid （RA） decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular triglyceride and serum alanine transaminase （ALT） and aspartate aminotransferase （AST） concentrations. Moreover, RA treatment improved glucose tolerance and insulin sensitivity in WT mice fed a HFD. However, these RA-induced effects in WT mice fed a HFD were alleviated in liver specific Sirtuin 1 （Sirtl） deficient （LKO）mice fed a HFD. Furthermore, RA also could not improve glucose tolerance and insulin sensitivity in LKO mice fed a HFD. The mechanism studies indicated that RA indeed increased the expression of hepatic S irtl and superoxide dismutase 2 （Sod2）, and inhibited the expression of sterol regulatory element binding protein 1 c （Srebp- 1 c） in WT mice in vivo and in vitro. RA decreased mitochondrial reactive oxygen species （ROS） production in WT primary hepatocytes and increased mitochondrial DNA （mtDNA） copy number in WT mice liver. However, these RA-mediated molecular effects were also abolished in the liver and primary hepatocytes from LKO mice. In summary, RA protected against HFD-induced hepatosteatosis by decreasing Srebp-1 c expression and improving antioxidant capacity through a S irt 1-mediated mechanism.展开更多
In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have...In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have been transfected with GST-pi cDNA inserted retrovirus vector, pXT1, and then G418 resistant clones have been analyzed by Southern and Northern analyses. NIH3T3/pXGST clones that stably express GST-pi and control cells,展开更多
The expression of rat Glutathione S-transferase P (GST-P) gene can be induced by many kinds of chemical inducers. We have studied the mechanisms of the expression of GST-P gene induced by 3 kinds of Chemical inducers ...The expression of rat Glutathione S-transferase P (GST-P) gene can be induced by many kinds of chemical inducers. We have studied the mechanisms of the expression of GST-P gene induced by 3 kinds of Chemical inducers using the induction of the gene expression by chemical inducers, transient transfection, reporter gene assays, electrophoretic mobility shift assays (EMSA) and Northern blot analysis. The results indicate that the effects and mechanisms of chemical inducers on the expression of GS7'-Pgene are different. The interaction of AP-1 or other corresponding transcription factors activated by phorbol ester (TPA) or glycidyl methatylate (GMA) and GPEl enhancer element induces the expression of GST-P gene, while some unknown factors activated by H2O2 interact with GPEII enhancer element.展开更多
基金supported by the National Natural Science Foundation of China (31371191)
文摘In this study, treatment of C57BL/6J （wild type, WT） mice fed a high-fat diet （HFD） with retinoic acid （RA） decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular triglyceride and serum alanine transaminase （ALT） and aspartate aminotransferase （AST） concentrations. Moreover, RA treatment improved glucose tolerance and insulin sensitivity in WT mice fed a HFD. However, these RA-induced effects in WT mice fed a HFD were alleviated in liver specific Sirtuin 1 （Sirtl） deficient （LKO）mice fed a HFD. Furthermore, RA also could not improve glucose tolerance and insulin sensitivity in LKO mice fed a HFD. The mechanism studies indicated that RA indeed increased the expression of hepatic S irtl and superoxide dismutase 2 （Sod2）, and inhibited the expression of sterol regulatory element binding protein 1 c （Srebp- 1 c） in WT mice in vivo and in vitro. RA decreased mitochondrial reactive oxygen species （ROS） production in WT primary hepatocytes and increased mitochondrial DNA （mtDNA） copy number in WT mice liver. However, these RA-mediated molecular effects were also abolished in the liver and primary hepatocytes from LKO mice. In summary, RA protected against HFD-induced hepatosteatosis by decreasing Srebp-1 c expression and improving antioxidant capacity through a S irt 1-mediated mechanism.
文摘In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have been transfected with GST-pi cDNA inserted retrovirus vector, pXT1, and then G418 resistant clones have been analyzed by Southern and Northern analyses. NIH3T3/pXGST clones that stably express GST-pi and control cells,
文摘The expression of rat Glutathione S-transferase P (GST-P) gene can be induced by many kinds of chemical inducers. We have studied the mechanisms of the expression of GST-P gene induced by 3 kinds of Chemical inducers using the induction of the gene expression by chemical inducers, transient transfection, reporter gene assays, electrophoretic mobility shift assays (EMSA) and Northern blot analysis. The results indicate that the effects and mechanisms of chemical inducers on the expression of GS7'-Pgene are different. The interaction of AP-1 or other corresponding transcription factors activated by phorbol ester (TPA) or glycidyl methatylate (GMA) and GPEl enhancer element induces the expression of GST-P gene, while some unknown factors activated by H2O2 interact with GPEII enhancer element.
