Altered expression of the neuropeptide-processing enzyme carboxypeptidase E in the rat brain after global ischemia

Carboxypeptidase E, an exoprotease involved in the processing of bioactive peptides released by a regulated secretory pathway, was identified in a sub tractive complementary DNA library derived from an ischemic rat brain by di fferential screening. In situ hybridization and immunocytochemical analysis showed the presence of carboxypeptidase E messenger RNA and protein in the cerebral cortex, thalamus, striatum, and hippocampus of a healthy rat brai n. After 15 minutes of transient global ischemia followed by 8 hours of rep erfusion, increased levels of carboxypeptidase E messenger RNA and protein were observed in the hippocampal CAI and CA3 regions and in the cortex, as detected by Northern and Western blot analyses and in situ hybridization. A fter extended reperfusion (24 to 72 hours), both carboxypeptidase E messeng er RNA and protein levels were decreased. The ischemia-induced changes in c arboxypeptidase E expression suggest that this enzyme may play a role in mo dulating the brain's response to ischemia.