Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17β-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS- hOGG1 ) on HeLa cells exposed to 2-ME. MTS- hOGG1 -expressing cells expos...

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Vydáno v:	Oncogene Ročník 27; číslo 26; s. 3710 - 3720
Hlavní autoři:	Chatterjee, A, Chang, X, Nagpal, J K, Chang, S, Upadhyay, S, Califano, J, Trink, B, Sidransky, D
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 12.06.2008 Nature Publishing Nature Publishing Group
Témata:	17β-Estradiol 8-Hydroxyguanine Ageing, cell death Apoptosis Apoptosis - drug effects Biological and medical sciences Caspase-3 Caspases - physiology Cell Biology Cell cycle Cell Cycle - drug effects Cell physiology Cell Survival - drug effects Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cerulenin Deoxyribonucleic acid DNA DNA Damage DNA glycosylase DNA Glycosylases - physiology Estradiol Estradiol - analogs & derivatives Estradiol - pharmacology Estrogens Fundamental and applied biological sciences. Psychology Genetics HeLa Cells Human Genetics Humans Hyperpolarization Internal Medicine Medicine Medicine & Public Health Membrane potential Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondrial DNA Molecular and cellular biology Oncology original-article Physiological aspects Poly(ADP-ribose) Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerases - metabolism Ribose United States activation mitochondria 2-methoxyestradiol Human Targeting Enzyme Fas activation Activation Carcinogenesis Glycosylases Mitochondria hOGG1 DNA Hydrolases Apoptosis
ISSN:	0950-9232, 1476-5594, 1476-5594
On-line přístup:	Získat plný text
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Popis
Shrnutí:	2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17β-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS- hOGG1 ) on HeLa cells exposed to 2-ME. MTS- hOGG1 -expressing cells exposed to 2-ME showed increased cellular survival and had significantly less G 2 /M cell cycle arrest compared to vector-only-transfected cells. In addition, 2-ME exposure resulted in an increase in mitochondrial membrane potential, increased apoptosis, accompanied by higher activation of caspase-3, -9, cleavage of Bid to tBid and protein poly(ADP-ribose) polymerase (PARP) cleavage in HeLa cells lacking MTS- hOGG1 . Fas inhibitors cerulenin or C75 inhibited 2-ME-induced caspase activation, PARP cleavage, apoptosis and reversed mitochondrial membrane hyperpolarization, thereby recapitulating the increased expression of MTS- hOGG1 . Hence, MTS- hOGG1 plays an important protective role against 2-ME-mediated mitochondrial damage by blocking apoptosis induced through the Fas pathway.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0950-9232 1476-5594 1476-5594
DOI:	10.1038/onc.2008.3