Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41.
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.
Adamson
D C
DC
Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, MD 21287, USA. valina.dawson@qmail.bs.jhu.edu
Wildemann
B
B
Sasaki
M
M
Glass
J D
JD
McArthur
J C
JC
Christov
V I
VI
Dawson
T M
TM
Dawson
V L
VL
D015526:AIDS Dementia Complex / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1; D006801:Humans; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D051381:Rats
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase