The effect of global ischemia and recirculation of rat brain on protein synthesisin vitro

Abstract

Transient cerebral ischemia causes long-lasting inhibition of protein synthesis despite recovery of energy metabolism. We investigated the question if this inhibition is due to the formation of a suppression factor which interferes with the function of the protein synthesizing machinery. For this purpose rats were submitted to 20 minutes four vessel-occlusion followed by recirculation times from 30 minutes to 7 days. Post-mitochondrial supernatant (PMS) from various brain regions was added to a self-contained, cell-free rabbit reticulocyte translational system, and the effect onin vitro protein synthesis was assessed by measuring¹⁴C-leucine incorporation over a duration of 45 minutes. PMS prepared at the end of ischemia from hippocampus, striatum and cerebellum inhibitedin vitro protein synthesis by 40%–60% but there was only a minor inhibition by PMS from cerebral cortex. During post-ischemic recirculation cortical PMS transiently induced inhibition ofin vitro protein synthesis by 30% but this effect gradually disappeared within one week. The inhibition caused by PMS from hippocampus, striatum and cerebellum was not reversed during recirculation and still amounted to about 40% after 7 days. Inhibition ofin vitro protein synthesis could be blocked by heating PMS to 100°C, indicating that the suppressor factor is a protein. The comparison of thein vitro effect of postischemic PMS with previously describedin vivo inhibition of protein synthesis demonstrates that the here observed suppressor factor is not able to explain the overall disturbance of protein synthesisin vivo. However, the inhibitory potency of this factor after as long as 7 days after recirculation points to an ongoing pathological process, the importance of which remains to be clarified.