17 β-estradiol inhibits H2O2-induced senescence in HUVEC cells through upregulating SIRT3 expression and promoting autophagy.

In this study, we examined the roles of SIRT3 in 17β-E2-induced autophagy and 17β-E2-mediated inhibition of hydrogen peroxide (H2O2)-induced senescence in Human umbilical vein endothelial cells (HUVEC). Cellular senescence was measured by immunoblot analysis with antibodies against phosphorylated Rb and senescence-associated β-galactosidase staining. Immunoblot analysis with antibodies against LC3 and p62 was performed to determine autophagy flux. Our findings show that 17β-E2 activates SIRT3 promoter and upregulates SIRT3 gene expression in HUVEC cells. siRNA-mediated silencing of SIRT3 gene expression inhibits 17β-E2-induced processing of LC3-I to LC3-II and degradation of p62, two widely-used makers of autophagy. SIRT3 knockdown also blocks 17β-E2-induced inhibition of cellular senescence triggered by H2O2. Our data further reveal that SIRT3 knockdown impairs 17β-E2-induced co-localization of LC3 and VDAC1, a marker protein on mitochondria, when HUVEC cells were co-treated with H2O2. Together, our findings suggest that 17β-E2 upregulates SIRT3 gene expression by activating SIRT3 promoter and then promotes autophagy, which in turn serves to remove dysfunctional mitochondria caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells. PMID: 32172411 [PubMed - as supplied by publisher]
Source: Biogerontology - Category: Geriatrics Authors: Tags: Biogerontology Source Type: research