Cytotoxic effect of HIV-1 coat glycoprotein gp120 on human neuroblastoma CHP100 cells involves activation of the arachidonate cascade.
HIV type-1 (HIV-1) coat glycoprotein gp120 causes necrotic death in human neuroblastoma CHP100 cells. Here, we investigated the possible role of the arachidonate cascade and membrane peroxidation in gp120-induced cell necrosis. It is shown that gp120 increases the intracellular concentrations of prostaglandin E2 and leukotriene B4 by up-regulating the activity and expression of the arachidonate-metabolizing enzymes prostaglandin H synthase and 5-lipoxygenase respectively. Consistent with this observation, selective inhibitors of prostaglandin H synthase (i.e. indomethacin) and 5-lipoxygenase (i.e. MK886 and caffeic acid) protected CHP100 cells against gp120-induced necrosis. Treatment with gp120 also enhanced membrane lipid peroxidation and this may be implicated in the execution of cell damage. Interestingly, incubation with exogenous nitric oxide (NO) mimicked the effects of gp120 on necrotic death of CHP100 cells and activation of prostaglandin H synthase and 5-lipoxygenase. This suggests that NO might participate in the mechanism by which gp120 activates the arachidonate cascade.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Via di Tor Vergata 135, I-00133 Rome, Italy.
Navarra
M
M
Corasaniti
M T
MT
Nisticò
G
G
Finazzi Agrò
A
A
D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015699:HIV Envelope Protein gp120; D007975:Leukotriene B4; D016718:Arachidonic Acid; D009569:Nitric Oxide; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone