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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1078-1085
IMMUNOBIOLOGY
Antiapoptotic mechanism of HIV protease inhibitors:
preventing mitochondrial transmembrane potential loss
Barbara N. Phenix,
Julian
J. Lum,
Zelin Nie,
Jaime Sanchez-Dardon, and
Andrew D. Badley
From the Ottawa Hospital Research Institute, University
of Ottawa; and the Division of Infectious Diseases, Ottawa
Hospital-General Campus, Ottawa, ON, Canada.
Treatment of cells with the HIV drugs ritonavir, saquinavir, or
nelfinavir (Nfv) inhibits apoptosis induced by a variety of stimuli. Because these drugs are protease inhibitors, they have been
postulated to inhibit apoptosis by blocking caspase activity. This
study shows that Nfv has no effect on caspase activity or on the
transcription or synthesis of a variety of apoptosis regulatory molecules. Instead, Nfv inhibits mitochondrial transmembrane potential loss (  m) and the subsequent release of apoptotic
mediators. Consequently, the antiapoptotic effects of Nfv are
restricted to apoptotic pathways that involve
m.
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