Evidence for a role of protein tyrosine kinases in cell death induced by gp120 in CHP100 neuroblastoma cells.
HIV-1 coat protein gp120 is able to kill neuronal cells in culture. Here we address the possible role of protein tyrosine kinases (PTKs) in gp120-induced neurotoxicity using the CHP100 human neuroblastoma cell line as experimental model. For this purpose, the effect of specific PTK inhibitors like genistein, herbimycin A and lavendustin A was evaluated on CHP100 cell death elicited by the viral protein. Here we report that genistein (1-10 microM) significantly reduced the cytotoxic effects induced by gp120 (10 pM). The same protective action was offered by a pre-treatment with herbimycin A (0.1-1 microM) or lavendustin A (1-10 microM). Conversely, daidzein (1-100 microM), a genistein analogue devoid of PTK inhibitory properties, failed to reduce CHP100 cell death caused by gp120. These findings suggest that PTKs can be involved in the signal transduction cascade by which the glycoprotein induces neurotoxicity.
Russo
Rossella
R
Department of Pharmacobiological Sciences, Faculty of Pharmacy, University 'Magna Graecia' of Catanzaro & ISN-CNR, Complesso 'Nini; Barbieri', 88021 Roccelletta di Borgia, Catanzaro, Italy.
Navarra
Michele
M
Rotiroti
Domenicantonio
D
Di Renzo
Gianfranco
G
D016227:Benzoquinones; D016923:Cell Death; D019833:Genistein / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D009447:Neuroblastoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D015699:HIV Envelope Protein gp120; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D010636:Phenols; D011809:Quinones; D017828:Rifabutin; C062898:lavendustin A; C004742:daidzein; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases