Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor
| Autor: | Heather Hardin, Rolf P. G. van Heeswijk, Andrew D. Badley, Joel G.R. Weaver, Bogdan Zurakowski, Valerie L. Sim, Sheng T. Hou, Barbara N. Phenix, Peter J. Wettstein, Guido Kroemer, Catherine Brenner, Aurélien Deniaud, Agathe Tarze, Gary D. Bren, Morgane LeBras, Li Dong, Jessica Lallier, Andre G. Douen, Romano T. Kroemer, Tia C. Moffat, David H. Lynch, Susan X. Jiang, Mario Y. Morin, Steffany A. L. Bennett |
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| Přispěvatelé: | Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Begue, Angelique |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular medicine.medical_treatment Apoptosis Pharmacology Antibodies Hepatitis Jurkat Cells Mice 03 medical and health sciences 0302 clinical medicine immune system diseases In vivo medicine Animals Humans HIV Protease Inhibitor [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] 030304 developmental biology Mice Inbred BALB C 0303 health sciences Nelfinavir Ritonavir Protease biology Adenine nucleotide translocator virus diseases HIV Protease Inhibitors General Medicine biochemical phenomena metabolism and nutrition Shock Septic Molecular biology [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] 3. Good health Mice Inbred C57BL Stroke Disease Models Animal Mitochondrial permeability transition pore biology.protein Female Mitochondrial ADP ATP Translocases 030217 neurology & neurosurgery Research Article Signal Transduction medicine.drug |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2005, 115, pp.1828-1838 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci22954 |
| Popis: | Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex. |
| Databáze: | OpenAIRE |
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