Estradiol ameliorates antioxidant axis SIRT1-FoxO3a-MnSOD/catalase in the heart of fructose-fed ovariectomized rats

Abstract

Harmful effects of fructose-rich diet (FRD) were predominantly observed in males, suggesting protective effects of estrogens. Little is known about AMPK/sirtuin-1 (SIRT1)/forkhead box O3 (FoxO3a)/manganese superoxide dismutase (MnSOD)/catalase signaling in the heart in state of metabolic syndrome and oxidative stress induced by fructose over-consumption. We investigated the effect of 10% FRD on expression of AMPK-SIRT1-FoxO3a-MnSOD/catalase axis in myocardium and potentially beneficial effect of 17β-estradiol replacement. The expression of NADPH oxidase 4 (Nox4) and miRNA-155, unfavorable regulators of this axis, were also investigated. FRD significantly increased AMPK and decreased FoxO3a activity, decreased SIRT1, MnSOD and Nox4 protein expression while E2 reverted these changes, except for Nox4, and increased catalase protein level. E2 diminished Nox4 and MnSOD mRNA level in FRD ovariectomized rats. These results suggest independent response of AMPK and SIRT to FRD treatment. The proposed signaling in the heart should be further investigated in the prooxidative and antioxidative milieu.