Transduction signals induced in rat brain cortex astrocytes by the HIV-1 gp120 glycoprotein.
Cultures of rat brain cortex astrocytes were exposed to 10(-10)-10(-9)M of the HIV-1 envelope glycoprotein, gp120. No specific binding was revealed by the iodinated protein, suggesting expression of only a few sites onto the cells. In contrast, two transduction signals were rapidly induced by gp120: increased tyrosine phosphorylation of a approximately 56 kDa protein and increased [Ca2+]i. This latter effect, present in 1/3 of the investigated astrocytes, consisted in: discrete or biphasic peaks; slowly rising plateaus; and various types of oscillations. Moreover, in apparently unresponsive cells [Ca2+]i rose slowly (45 min) to double the resting levels. Rat brain cortex astrocytes thus appear highly sensitive to gp120. The induced array of signals might contribute to neurotoxicity during HIV infection.
Codazzi
F
F
Department of Pharmacology, University of Milano, Italy.
Racchetti
G
G
Grohovaz
F
F
Meldolesi
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D002614:Chelating Agents; D015699:HIV Envelope Protein gp120; D009419:Nerve Tissue Proteins; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium