Induction of apoptosis by a nonnucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitor.
Inhibition of human immunodeficiency virus type 1 reverse transcriptase (RT) by both nucleoside and nonnucleoside RT inhibitors profoundly inhibits virus replication. Nucleoside RT inhibitors are known to be toxic, but there is little information regarding the toxicities of nonnucleoside RT inhibitors (NNRTI). We demonstrate that efavirenz (an NNRTI) induces caspase- and mitochondrion-dependent apoptosis of Jurkat T cells and human peripheral blood mononuclear cells. The clinical relevance of these observations is not yet clear.
Pilon
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HIV Research Laboratory, Ottawa Health Research Institute, Ottawa, Ontario, Canada K1H 8L6.
Lum
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Sanchez-Dardon
J
J
Phenix
B N
BN
Douglas
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Badley
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AD
D000480:Alkynes; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D048588:Benzoxazines; D020169:Caspases / Q000502:physiology; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D010078:Oxazines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D000480:Alkynes; D017304:Annexin A5; D048588:Benzoxazines; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate; C098320:efavirenz