THE PYRUVATE-DEHYDROGENASE COMPLEX IS PARTIALLY INACTIVATED DURING EARLY RECIRCULATION FOLLOWING SHORT-TERM FOREBRAIN ISCHEMIA IN RATS

The mechanisms of selective neuronal loss after short-term global isch emia remain undefined, but processes including increased proteolytic a ctivity, impaired protein synthesis, and oxidative damage have been pr oposed to contribute. A decrease in activity of the pyruvate dehydroge nase complex in the dorsolateral striatum, an ischemia-susceptible reg ion, is one change apparently differentiating this region from ischemi a-resistant areas during early recirculation, To provide an insight in to processes contributing to postischemic cell damage, the changes in the pyruvate dehydrogenase complex during early recirculation have bee n further characterized. These studies provide clear confirmation that the activity of the pyruvate dehydrogenase complex is reduced in mito chondria from the dorsolateral striatum by 3 h of recirculation. The d ecrease in activity was not accompanied by a loss of antigenic sites o r by changes in electrophoretic mobility of the components of the comp lex. A reduction in activity of the E1 component of the complex (39-42 % decrease), but not the E2 and E3 components, was observed that was a pparently sufficient to explain the decrease in activity of the whole complex. These results indicate that the changes in activity of the py ruvate dehydrogenase complex in the dorsolateral striatum are not due to loss or gross disruption of the constituent proteins but rather mos t likely reflect a selective inactivation of a specific component of t he complex.