Neuronal Apoptosis induced by HIV-1 Tat Protein and TNF-a: Potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.

BIN SHI; JAY RAINA; ALFREDO LORENZO; JORGE BUSCIGLIO; DANA GABUZDA

TAYLOR & FRANCIS INC

Año: 1998 vol. 4 p. 281 - 281

poptosis of neurons and non-neuronal cells has been demonstrated in the brain of AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli are likely to be soluble factors. Several candidates for the soluble factors that lead to neuronal apoptosis in HIV-1 infection have been proposed, including the HIV-1 Tat protein and TNF-a. The mechanisms that lead to neuronal apoptosis in the brain ofAIDS patients in vivo,may involve the combined effects of more than one pro-apoptotic factor. In this study, we examine whether exposure of primary human neurons to the combination of HIV-1 Tat and TNF-a can potentiate the induction of neuronal apoptosis compared with exposure to either factor alone. TNF-a was shown to potentiate the induction of neuronal apoptosis byHIV-1 Tat via amechanismthat involves increased oxidative stress. Antioxidants inhibited, but did not completely abolish the induction of neuronal apoptosis by Tat, suggesting that other mechanisms are