| Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis. | |
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MedLine Citation:
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PMID: 18246124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17beta-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. |
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Authors:
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A Chatterjee; X Chang; J K Nagpal; S Chang; S Upadhyay; J Califano; B Trink; D Sidransky |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-02-04 |
Journal Detail:
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Title: Oncogene Volume: 27 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-12 Completed Date: 2008-07-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 3710-20 Citation Subset: IM |
Affiliation:
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Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Caspases / physiology Cell Cycle / drug effects Cell Survival / drug effects DNA Damage DNA Glycosylases / physiology* Estradiol / analogs & derivatives*, pharmacology Hela Cells Humans Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects* Poly(ADP-ribose) Polymerases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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5-PO1CA 77664/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/oxoguanine glycosylase 1, human; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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