1. Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41.
- Author
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Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, and Dawson VL
- Subjects
- AIDS Dementia Complex metabolism, Animals, Brain metabolism, Cell Death, Cells, Cultured, Cerebral Cortex enzymology, Cerebral Cortex metabolism, Enzyme Induction, HIV Envelope Protein gp120 metabolism, HIV Envelope Protein gp120 pharmacology, HIV Envelope Protein gp41 pharmacology, Humans, Neuroglia cytology, Neurons cytology, Nitric Oxide metabolism, Nitric Oxide Synthase genetics, Polymerase Chain Reaction, Rats, AIDS Dementia Complex enzymology, Brain enzymology, HIV Envelope Protein gp41 metabolism, HIV-1, Nitric Oxide Synthase biosynthesis
- Abstract
Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.
- Published
- 1996
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