17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.
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.
['Batnasan|Enkhzaya|E|', 'Wang|Ruoxi|R|', 'Wen|Jitao|J|', 'Ke|Yueshuang|Y|', 'Li|Xiaoxue|X|', 'Bohio|Ameer Ali|AA|', 'Zeng|Xianlu|X|', 'Huo|Hongliang|H|', 'Han|Liping|L|', 'Boldogh|Istvan|I|', 'Ba|Xueqing|X|']
D021581:Active Transport, Cell Nucleus D000975:Antioxidants D017209:Apoptosis D051033:Apoptosis Inducing Factor D001943:Breast Neoplasms D002466:Cell Nucleolus D019610:Cytoprotection D053938:DNA Fragmentation D004305:Dose-Response Relationship, Drug D004789:Enzyme Activation D004958:Estradiol D047628:Estrogen Receptor alpha D005260:Female D006801:Humans D006861:Hydrogen Peroxide D061986:MCF-7 Cells D018384:Oxidative Stress D000071137:Poly (ADP-Ribose) Polymerase-1 D034622:RNA Interference D015398:Signal Transduction D013997:Time Factors D014162:Transfection
AIF Nucleolus Cell death Estrogen PARP1