Astrocyte apoptosis induced by HIV-1 transactivation of the c-kit protooncogene

Jianglin He, Carlos M. Decastro, George R. Vandenbark, Jorge Busciglio, Dana Gabuzda

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

HIV-1 infection of the central nervous system (CNS) frequently causes dementia and other neurological disorders. The mechanisms of CNS injury in HIV-1 infection are poorly understood. Apoptosis of neurons and astrocytes is induced by HIV-1 infection in vitro and in brain tissue from AIDS patients, but the apoptotic stimuli have not been identified. We report herein that HIV-1 infection of primary brain cultures induces the receptor tyrosine kinase protooncogene c-kit and that high levels of c-Kit expression are associated with astrocyte apoptosis. Overexpression of c-Kit in an astrocyte- derived cell line in the absence of HIV-1 induces rapid apoptotic death. The apoptotic mechanism requires the c-Kit tyrosine kinase domain. The mechanism of c-kit induction by HIV-1 involves transactivation of the c-kit promoter by the HIV-1 Nef protein. These studies demonstrate that c-Kit can induce astrocyte apoptosis and suggest that this mechanism may play a role in CNS injury caused by HIV-1 infection. We propose that c-Kit can serve dual functions as a growth factor receptor or apoptosis inducer.

Original languageEnglish
Pages (from-to)3954-3959
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number8
DOIs
StatePublished - 15 Apr 1997

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