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 gp120 causes delayed programmed cell death (apoptosis) in rat brain neocortex. Here, we investig ated the possible role of the arachidonate cascade and membrane peroxidatio n in this process. it is shown that gp120 causes a rapid increase in the ac tivity and expression of the arachidonate-metabolizing enzyme prostaglandin H synthase, paralleled by increased prostaglandin E-2 levels. The selectiv e inhibitor of prostaglandin H synthase indomethacin inhibited enzyme activ ity, reduced prostaglandin E-2 content, and partially protected neocortex a gainst gp120-induced apoptosis. Conversely, the activity and expression of the arachidonate-metabolizing enzyme 5-lipoxygenase decreased upon gp120 tr eatment, as well as the level of its product, leukotriene B-4. Treatment wi th gp120 also reduced membrane lipid peroxidation, and this may be implicat ed in the execution of programmed cell death. These results suggest that ea rly derangement of the arachidonate cascade in favor of prostanoids may be instrumental in the execution of delayed apoptosis in the brain neocortex o f rats.