Ginseng increases Klotho expression by FoxO3-mediated manganese superoxide dismutase in a mouse model of tacrolimus-induced renal injury.
The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.
['Lim|Sun Woo|SW|', 'Shin|Yoo Jin|YJ|', 'Luo|Kang|K|', 'Quan|Yi|Y|', 'Cui|Sheng|S|', 'Ko|Eun Jeong|EJ|', 'Chung|Byung Ha|BH|', 'Yang|Chul Woo|CW|']
D000375:Aging D000818:Animals D000975:Antioxidants D065095:Calcineurin Inhibitors D002460:Cell Line D004195:Disease Models, Animal D000071316:Forkhead Box Protein O3 D005966:Glucuronidase D006801:Humans D007668:Kidney D000090265:Klotho Proteins D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008928:Mitochondria D005894:Panax D008517:Phytotherapy D051436:Renal Insufficiency, Chronic D015398:Signal Transduction D013482:Superoxide Dismutase D016559:Tacrolimus
ginseng Klotho oxidative stress tacrolimus mitochondria MnSOD