Ischemia induces a selective biphasic response in brain mitochondrial mRNAlevels

WE determined the independent effects of hypoxia, glucose deprivation and i schemia (hypoxia plus glucose deprivation) on steady-state levels of mRNA c oding for specific nuclear and mitochondrially encoded enzymes of oxidative metabolism in cultured rat neurons and glia. Neither hypoxia nor low gluco se alone changed steady-state message levels for any transcript. However, i schemia induced a biphasic effect on mitochondrially encoded transcripts fo r cytochrome oxidase subunit two (CO2) and the subunits 8 and 6 of ATPase ( A 8/6), initially decreasing and then increasing mRNA levels to or above th e levels recorded prior to ischemia. In contrast, three nuclear encoded tra nscripts for mitochondrial proteins were decreased by ischemia. These data demonstrate a lack of coordination between the expression of nuclear and mi tochondrial genes in the initial response to ischemia and suggest that a se lective, primary reaction to brain cell insults exists within the mitochond rion. NeuroReport 10:1593-1598 (C) 1999 Lippincott Williams & Wilkins.