Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 7, Pages 1828-1838Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI22954
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Funding
- NIAID NIH HHS [R01 AI062261, R01 AI62261-01-1, R01 AI40384, R01 AI040384] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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.
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