HIV-1 gp120 and NMDA induce protein kinase C translocation differentially in rat primary neuronal cultures.
Exposure of rat cortical neurons to the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 in vitro causes a rise in the intracellular Ca2+ level and a subsequent translocation of protein kinase C (PKC) from the cytosol to the membrane. Such a translocation persists for at least 2 h, but only in cultures with media not depleted of endogenous glutamate. Enzymatic degradation of glutamate in the medium by the enzyme glutamate-pyruvate transaminase (GPT) abolishes the long-lasting effect of gp120 on the association state of PKC; under this incubation condition the translocation period is < 1 h. Memantine and the ganglioside GM1 prevent N-methyl D-aspartate receptor-mediated long-term translocation of PKC and gp120-mediated neurotoxicity (in the absence of GPT); they have no effect on short-term translocation of PKC. We suggest that gp120-caused neuronal death involves an indirect sensitization step of the NMDA receptors, which ultimately induces neuronal death.
Ushijima
H
H
Division of AIDS Virus, National Institute of Health, Tokyo, Japan.
Ando
S
S
Kunisada
T
T
Schröder
H C
HC
Klöcking
H P
HP
Kijjoa
A
A
Müller
W E
WE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics*; D007425:Intracellular Membranes / Q000378:metabolism; D008559:Memantine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D014178:Translocation, Genetic / Q000187:drug effects*
D015699:HIV Envelope Protein gp120; D016194:Receptors, N-Methyl-D-Aspartate; D005677:G(M1) Ganglioside; D016202:N-Methylaspartate; D011493:Protein Kinase C; D002118:Calcium; D008559:Memantine