Antioxidants inhibit stimulation of HIV transcription.
In studies presented here, we demonstrate that antioxidants regulate NF-kappa B activation and signal transduction pathways leading to HIV expression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant and an efficient glutathione (GSH) precursor, inhibits NF-kappa B activation and HIV expression under conditions in which GSH is depleted and NAC cannot be converted to GSH, (2) that the D-stereoisomer of NAC and a wide variety of chemically unrelated antioxidants also inhibit NF-kappa B activation and/or transcription directed by the HIV LTR, and (3) that depletion of GSH, the principal intracellular antioxidant, augments HIV production in an acute infection model. Taken together, these findings suggest direct antioxidant action as the mechanism for inhibition of HIV transcription by NAC. They also confirm that GSH, acting in its capacity as an antioxidant, regulates HIV expression and that exogenous antioxidants can potentiate this regulation.
Staal
F J
FJ
Department of Genetics, Stanford University School of Medicine, California 94305.
Roederer
M
M
Raju
P A
PA
Anderson
M T
MT
Ela
S W
SW
Herzenberg
L A
LA
Herzenberg
L A
LA
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016325:HIV Long Terminal Repeat; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000975:Antioxidants; D016328:NF-kappa B; D012694:Serine; D005978:Glutathione; C012162:N-acetylserine; D000111:Acetylcysteine