Oxygen deprivation following cessation of blood flow to vital organs such as brain, heart, and kidney is a ubiquitous human disease, invariably leading to devastating consequences. Studies in experimental models support the contention that membrane permeability is altered, ion fluxes impaired, and energy stores depleted under these circumstances. Certain
lipids such as
diglycerides (DG) and
arachidonic acid (AA), both of which are important cellular second messengers, appear to increase during
ischemia. At this point, the contribution of these and other
lipids to cell deregulation, loss of function, and ultimate death has not been clarified because no precise link between
lipid alterations as detected in
ischemia and subsequent cellular processes has been made. In this report we examine the origin of
lipid-derived second messengers in fetal rat brain prelabeled with [3H]AA and study the fate of various
lipids upon obstruction of the fetal-maternal circulation. The data support the possibility of a
phospholipase A2-mediated deacylation of poly-
phosphoinositides (poly-PI) to form free AA and a
phospholipase C-mediated hydrolysis of PC to form DG during
ischemia.