HIV-1 coat glycoprotein gp120 induces apoptosis in rat brain neocortex by deranging the arachidonate cascade in favor of prostanoids.
Human immunodeficiency virus type-1 coat glycoprotein gp 120 causes delayed programmed cell death (apoptosis) in rat brain neocortex. Here, we investigated the possible role of the arachidonate cascade and membrane peroxidation in this process. It is shown that gp 120 causes a rapid increase in the activity and expression of the arachidonate-metabolizing enzyme prostaglandin H synthase, paralleled by increased prostaglandin E(2) levels. The selective inhibitor of prostaglandin H synthase indomethacin inhibited enzyme activity, reduced prostaglandin E(2) content, and partially protected neocortex against gp 120-induced apoptosis. Conversely, the activity and expression of the arachidonate-metabolizing enzyme 5-lipoxygenase decreased upon gp 120 treatment, as well as the level of its product, leukotriene B(4). Treatment with gp 120 also reduced membrane lipid peroxidation, and this may be implicated in the execution of programmed cell death. These results suggest that early derangement of the arachidonate cascade in favor of prostanoids may be instrumental in the execution of delayed apoptosis in the brain neocortex of rats.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences. "Mondino-Tor Vergata" Center for Experimental Neurobiology, University of Rome "Tor Vergata," Rome, Italy.
Bari
M
M
Corasaniti
M T
MT
Nisticó
R
R
Bagetta
G
G
Finazzi-Agrò
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019579:Neocortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D015699:HIV Envelope Protein gp120; D011453:Prostaglandins; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin