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Neurotoxic Activity of the HIV-1 Envelope Glycoprotein: Activation of Protein Kinase C in Rat Astrocytes
Department of Pathobiology, School of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, USA
Department of Microbiology, University Alabama at Birmingham, Birmingham, AL 35294, USA
Department of Cell Biology, University Alabama at Birmingham, Birmingham, AL 35294, USA
* Author to whom correspondence should be addressed.
Received: 7 June 2002; Accepted: 30 October 2002 / Published: 30 November 2002
Abstract: Envelope glycoprotein (gp120) of the human immunodeficiency virus type one (HIV-1), has adverse effects on glial cells and neurons. This study reports on the direct effect of recombinant gp120 (r-gp120) produced from different expression systems on protein kinase C, as a measure of relative neurotoxicity. Brain cells were grown in vitro from explants of the cerebral cortex of newborn rats, and recombinant gp120 preparations expressed in mammalian cell/vaccinia virus and insect cell/baculovirus systems were applied to astrocyte-enriched cultures. The gp120 preparations activated protein kinase C (PKC) to similar levels in these cells. Mutant recombinant gp120 lacking the amino-terminal 29 amino acids produced from the mammalian and insect cells also activated PKC to similar levels as did the full-length protein. The recombinant proteins specifically activated PKC β and ζ, suggesting that they are able to induce both Ca2+-dependent and Ca2+-independent isoforms of this enzyme. Alteration of PKC activity in astrocytes by gp120 indicates its ability to modulate gene expression, which is associated with the neurotoxicity of this protein. Furthermore, the results suggest that the deletion of the first 29 residues of NH2-terminal end of the gp120 does not affect the functional activity of this protein with regard to modulation of signal transduction in astrocytes.
Keywords: HIV; gp120; astrocytes; baculovirus; recombinant; protein kinase C
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Adeyemo, O.; Wu, R.; Parker, S.; Benveniste, E.N.; Hunter, E.; Adebayo, I. Neurotoxic Activity of the HIV-1 Envelope Glycoprotein: Activation of Protein Kinase C in Rat Astrocytes. Int. J. Mol. Sci. 2002, 3, 1105-1116.
Adeyemo O, Wu R, Parker S, Benveniste EN, Hunter E, Adebayo I. Neurotoxic Activity of the HIV-1 Envelope Glycoprotein: Activation of Protein Kinase C in Rat Astrocytes. International Journal of Molecular Sciences. 2002; 3(11):1105-1116.
Adeyemo, Oyewole; Wu, Rong; Parker, Scott; Benveniste, Etty N.; Hunter, Eric; Adebayo, Isaac. 2002. "Neurotoxic Activity of the HIV-1 Envelope Glycoprotein: Activation of Protein Kinase C in Rat Astrocytes." Int. J. Mol. Sci. 3, no. 11: 1105-1116.