17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha

Enkhzaya Batnasan, Ruoxi Wang, Jitao Wen, Yueshuang Ke, Xiaoxue Li, Ameer Ali Bohio, Xianlu Zeng, Hongliang Huo, Liping Han, Istvan Boldogh, Xueqing Ba

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ERα and ERβ). Parthanatos was induced by challenging the cells with hydrogen peroxide (H2O2). Microscopic imaging and molecular biological techniques, such as Western blot analysis and RNA interference, were performed. The results showed 17β estradiol (E2) protected MCF7 cells from PARP1-dependent cell death by decreasing protein PARylation, and AIF translocation into nuclei/nucleoli. Down-regulation of ERα expression by siRNA before E2 addition resulted in the failure of the E2-mediated inhibition of H2O2-induced protein PARylation and AIF nucleolar translocation. Together these data suggest that estrogen via its alpha-type receptor inhibits oxidative stress-induced, PARP1-dependent cell death. The present study provided us insight into how to apply hormone therapy in intervention of parthanatos-implicated ischemic and degenerative diseases.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalToxicology Letters
Volume232
Issue number1
DOIs
StatePublished - Jan 5 2015

Keywords

  • AIF
  • Cell death
  • Estrogen
  • Nucleolus
  • PARP1

ASJC Scopus subject areas

  • Toxicology

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