17β‐Estradiol regulates the expression of antioxidant enzymes in myocardial cells by increasing Nrf2 translocation

Abstract

The transcription factor-E2-related factor 2 (Nrf2) is an important regulator against the process of oxidative stress. It can effectively scavenge oxygen-free radicals within cells to maintain homeostasis. In this study, we cultured primary myocardial cells, established the hypoxia/reoxygenation (H/R) model to simulate myocardial ischemia/reperfusion injury, and examined effects of 17β-estradiol (E2) on the quantitative changes of Nrf2 in cytosolic and nuclear extracts, the mRNA expression of heme oxygenase 1 (HO-1), superoxide dismutase (Cu/Zn-SOD), glutathione S transferase (GST), and glutamate cysteine ligase amide (GCL) of each model group by Western blot assays and reverse transcription polymerase chain reaction, to investigate the effects of E2 against H/R/ injury in cultured myocardial cells. The present study shows that E2 can upregulate Nrf2 in nuclear extracts and increase the expression of HO-1, Cu/Zn-SOD, GST, and GCL significantly during H/R injury. Hence, our present findings suggest that E2 exhibits its antioxidant role by upregulating Nrf2 in nuclear extracts.

The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice

“…Our results on the increased expression of HO-1 gene are in agreement with findings of Yu et al, [7] about E 2 effects of transcription factor Nrf2 on myocardial cells. These authors have shown a concomitant upregulation of the transcription factor Nrf2 in nuclear extracts.…”

“…Increased expression of HO-1 and several other antioxidant enzymes induced in myocardial cells by E 2 treatment was explained by increased nuclear translocation of transcription factor Nrf2 [7]. HO is the rate-limiting enzyme for heme degradation in mammals.…”

“…Although the effect of E 2 on HO-1 expression and its actions as an antioxidant have been well documented [6,7], currently there are no data about the in vivo influence of E 2 on sex-related HO-1 expression. Moreover, it is not known whether E 2 influences DPP III.…”

Nuclear Factor Erythroid 2-Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

“…Estrogen stimulates Nrf2 activation in epithelial cells of the mammary gland, cerebral nerve tissue, primary myocardial cells, umbilical vein endothelial cells, ovarian epithelial carcinoma, and breast cancer cells (Liao et al, 2012;Yu et al, 2012;Zhang et al, 2013b;Gorrini et al, 2014;Meng et al, 2014;Wu et al, 2014). In contrast, estrogen potently inhibits the activities of Nrf2 target proteins (glutathione-S-transferase and quinone reductase), specifically in the uterus, possibly via its liganddependent interaction with Nrf2 (Ansell et al, 2004(Ansell et al, , 2005.…”

Species and Tissue Differences in β-Estradiol 17-Glucuronidation

“…E2 has the potential to protect the liver, small intestine, and kidney against oxidative stress. 3,4) The expression of glutathione Stransferase 5) and superoxide dismutase 6) has been reported to be increased by E2, suggesting a possible antioxidant role mediated by the upregulation of antioxidant enzymes. Glucuronidation of E2 at the 17-hydroxy position is one of the major metabolic pathways, which functionally inactivates E2.…”