Apoptosis induced by HIV-gp120 in a Th1 clone involves the generation of reactive oxygen intermediates downstream CD95 triggering.
HIV-gp120 sensitizes Th1 clones from seronegative donors to apoptosis, which occurs through two distinct events: expression of CD95L followed by its interaction with CD95 to trigger cell death. gp120-apoptosis of the Th1 clone 103 was inhibited by Cyclosporin A, the PTK inhibitors Genistein and PNU152518, as well as the anti-oxidants Ascorbic Acid and Glutathione. Cyclosporin A interfered with CD95L expression, Ascorbic Acid and Glutathione inhibited cell death triggered by CD95/CD95L interaction; Genistein and PNU152518 acted on both steps. The occurrence of oxidative stress during CD95-dependent apoptosis was supported by the direct evidence of ROI production.
Radrizzani
M
M
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milano, Italy.
Accornero
P
P
Delia
D
D
Kurrle
R
R
Colombo
M P
MP
D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D053222:Fas Ligand Protein; D015870:Gene Expression; D019833:Genistein; D005978:Glutathione / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000378:metabolism / Q000502:physiology / Q000821:virology*; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D007529:Isoflavones; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D019014:fas Receptor; D016572:Cyclosporine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005978:Glutathione; D001205:Ascorbic Acid