INVESTIGADORES
LORENZO Alfredo Guillermo
artículos
Título:
Neuronal Apoptosis induced by HIV-1 Tat Protein and TNF-a: Potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.
Autor/es:
BIN SHI; JAY RAINA; ALFREDO LORENZO; JORGE BUSCIGLIO; DANA GABUZDA
Revista:
JOURNAL OF NEUROVIROLOGY
Editorial:
TAYLOR & FRANCIS INC
Referencias:
Año: 1998 vol. 4 p. 281 - 290
ISSN:
1355-0284
Resumen:
Apoptosis 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 also likely to be involved. These ®ndings suggest that soluble
HIV-1 Tat and TNF-a may play a role in neuronal apoptosis induced by HIV-1
infection of the CNS, particularly when present in combination. Our ®ndings
further suggest that one mechanism whereby combinations of pro-apoptotic
factorsmay potentiate the induction of neuronal apoptosis in the brain of AIDS
patients is by increasing oxidative stress. Understanding the role of oxidative
stress and othermechanisms that lead to apoptosis inHIV-1 infection of theCNS
may advance the development of new therapeutic strategies to prevent
neuronal cell death and improve neurologic function in AIDS patients.