Platelet-activating Factor Receptor Activation
Year: 1998
Type: article
Abstract: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system results in neuronal apoptosis. Activated HIV-1-infected monocytes secrete high levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the phospholipid mediator platelet-activating factor (PAF). TNF-alpha and PAF are elevated in the central nervous system of patients with HIV-1-associated dementia. We now demonstrate that conditioned media from activated HIV-1-infected monocytes induces neuronal apoptosis, which can be prevented by co-incubation with PAF acetylhydrolase, the enzyme that catabolizes PAF in the central nervous system. Preceding apoptosis is a TNF-alpha-induced increase in neuronal ceramide levels. TNF-alpha-mediated neuronal apoptosis can also be blocked by co-incubation with PAF acetylhydrolase, or a PAF receptor antagonist. Blocking pathologic activation of PAF receptors may therefore be a pivotal step in the treatment of HIV-1-associated dementia.
Source: Journal of Biological Chemistry
Authors: Seth W. Perry, Jason A. Hamilton, Larry W. Tjoelker, Ghassan Dbaibo, Kirk A. Dzenko, Leon G. Epstein, Yusuf Hannun, J. Steven Whittaker, Stephen Dewhurst, Harris A. Gelbard
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2060264243