Altered lipid metabolism in the presence and absence of extracellular Ca2+ during combined oxygen-glucose deprivation in primary astrocyte cultures.

Abstract

The effect of combined oxygen-glucose deprivation (COGD) on lipid metabolism in primary rat cortical astrocyte cultures was studied in both the presence and absence of extracellular Ca2+. In this study, increases in intracellular Ca2+ from internal Ca2+ stores were not inhibited nor were internal Ca2+ levels buffered. Combined oxygen-glucose deprivation resulted in a quantitative reduction in phospholipid levels and an increase in free fatty acid and lysophospholipid levels. Four hours after the onset of COGD, ethanolamine- and choline glycerophospholipid levels were decreased by 40 and 46% from control levels in the presence of Ca2+, respectively. A similar decrease was found 6 hr after onset of COGD in the absence of Ca2+. These changes were accompanied by elevated levels of the corresponding lysophospholipids. However, the increases in lysophospholipid content did not account for the entire loss of ethanolamine- or choline glycerophospholipid. Phosphatidylserine was reduced in both the presence and absence of extracellular Ca2+ but phosphatidylinositol was only decreased in the absence of Ca2+. Statistically significant increases in total fatty acid (FA) and polyunsaturated fatty acid (PUFA) levels occurred at 30 min and 3 hr after the onset of COGD in the absence and presence of Ca2+, respectively. Arachidonic acid levels were increased in both groups by 1 hr. These increases in FA, PUFA, and specifically arachidonic acid were time-dependent and increased over the 12 hr of COGD. Collectively, these results indicate the activation of an acylhydrolase mechanism in the possible presence of an inhibited reacylation pathway.(ABSTRACT TRUNCATED AT 250 WORDS)