Human immunodeficiency virus type-1 coat glycoprotein gp120 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 gp120 causes a rapid increase in the activity and expression of the arachidonate-metabolizing enzyme prostaglandin H synthase, paralleled by increased prostaglandin E2 levels. The selective inhibitor of prostaglandin H synthase indomethacin inhibited enzyme activity, reduced prostaglandin E2 content, and partially protected neocortex against gp120-induced apoptosis. Conversely, the activity and expression of the arachidonate-metabolizing enzyme 5-lipoxygenase decreased upon gp120 treatment, as well as the level of its product, leukotriene B4. Treatment with gp120 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.
|Number of pages||8|
|Journal||Journal of Neurochemistry|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience