| hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells. | |
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MedLine Citation:
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PMID: 21071633 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase holoenzyme. Evidence is accumulating to link hTERT to activities other than telomere maintenance and immortalization. Here, we show that hTERT overexpression not only reduces the basal cellular reactive oxygen species (ROS) levels but also inhibits endogenous ROS production in response to stimuli that induce intracellular ROS generation. Conversely, siRNA-mediated gene silencing of hTERT potentiated the increase in cellular ROS levels following exposure to oxidative stress. This antioxidant effect of hTERT is mediated via a significant increase in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as efficient recovery of the oxidized peroxiredoxin to its nonoxidized form. Our data also provide evidence for mitochondrial localization of hTERT, and a significantly higher activity of cytochrome C oxidase, the rate-limiting enzyme in the mitochondrial electron transport chain, in hTERT overexpressing cells. To ascertain whether the improved mitochondrial function and antioxidant effect of hTERT could provide cancer cells with a survival advantage, the effect of oxidative stress on mitochondrial apoptosis was evaluated. Indeed, hTERT overexpressing cells inhibited cytosolic acidification, translocation of Bax, the drop in mitochondrial transmembrane potential, the release of cytochrome C to the cytosol, and cell death. Taken together, these data demonstrate a hitherto undefined role of hTERT in alleviating cellular ROS levels by way of potentiating the cellular antioxidant defense systems, and in doing so endowing cancer cells with the ability to evade death stimuli. |
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Authors:
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Inthrani R Indran; Manoor P Hande; Shazib Pervaiz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-11 |
Journal Detail:
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Title: Cancer research Volume: 71 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 266-76 Citation Subset: IM |
Copyright Information:
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© 2010 AACR. |
Affiliation:
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Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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genetics* Electron Transport Complex IV / metabolism Flow Cytometry Glutathione Disulfide / metabolism Glutathione Peroxidase / metabolism Glutathione Reductase / metabolism Hela Cells Humans Neoplasms / metabolism, pathology* Oxidation-Reduction Reactive Oxygen Species / metabolism* Telomerase / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 27025-41-8/Glutathione Disulfide; EC 1.11.1.9/Glutathione Peroxidase; EC 1.8.1.7/Glutathione Reductase; EC 1.9.3.1/Electron Transport Complex IV; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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