title: 17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.
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.
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China.
authors.forename: Enkhzaya
authors.initials: E
authors.lastname: Batnasan
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China.
authors.forename: Jitao
authors.initials: J
authors.lastname: Wen
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China.
authors.forename: Yueshuang
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China; Institute of Genetics and Cytology, Changchun, 130024, China. Electronic address: baxq755@nenu.edu.cn.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China.
authors.forename: Ameer Ali
authors.initials: AA
authors.lastname: Bohio
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China; Institute of Genetics and Cytology, Changchun, 130024, China.
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
authors.affiliation: School of Life Science, Northeast Normal University, Changchun 130024, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Huo
authors.affiliation: Department of Bioscience, Changchun Normal University, Changchun 130032, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Changchun, 130024, China; Institute of Genetics and Cytology, Changchun, 130024, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
mesh_terms: D021581:Active Transport, Cell Nucleus; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002466:Cell Nucleolus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D061986:MCF-7 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: C494829:AIFM1 protein, human; D000975:Antioxidants; D051033:Apoptosis Inducing Factor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: AIF; Cell death; Estrogen; Nucleolus; PARP1