| Nelfinavir induces necrosis of 3T3F44-2A adipocytes by oxidative stress. | |
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MedLine Citation:
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PMID: 15577407 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Protease inhibitor treatment strongly diminishes mortality in HIV-infected patients. This treatment has also been associated with lipodystrophy and has been shown to alter adipocyte differentiation. The protease inhibitor nelfinavir has been indirectly implicated in the appearance and development of lipodystrophic syndrome, as well as in adipocyte cell death. The aim of this study was to evaluate the effects of nelfinavir on the 3T3-F442A adipocyte cell line. Nelfinavir (30 microM) induced cell death of 3T3-F442A adipocytes by a necrotic process that was not mediated by TNF-alpha. Treatment of cells with this protease inhibitor led to a significant increase in expression of the heme oxygenase-1 gene that could be reduced by 100 microM of the antioxidant ascorbate. Moreover, ascorbate had a protective effect on nelfinavir-induced necrosis, decreasing the percentage of necrotic cells by 70%. Our results show that nelfinavir induces necrosis of adipocytes mediated by a cellular increase of reactive oxygen species. This deleterious effect could be counterbalanced by ascorbate. |
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Authors:
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Stéphanie Vincent; Franck Tourniaire; Claire M El Yazidi; Emmanuel Compe; Olivier Manches; Richard Plannels; Régis Roche |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: 37 ISSN: 1525-4135 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-12-03 Completed Date: 2005-12-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States |
Other Details:
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Languages: eng Pagination: 1556-62 Citation Subset: IM; X |
Affiliation:
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INSERM 476 Unit, School of Medicine, Marseille, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Adipocytes / drug effects*, physiology Animals Apoptosis Ascorbic Acid / pharmacology Cell Line HIV Protease Inhibitors / pharmacology* Heme Oxygenase-1 / genetics, metabolism Mice Necrosis / chemically induced* Nelfinavir / pharmacology* Oxidative Stress / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/HIV Protease Inhibitors; 159989-64-7/Nelfinavir; 50-81-7/Ascorbic Acid; EC 1.14.99.3/Heme Oxygenase-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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