Altered association of protein tyrosine kinases with postsynaptic densities after transient cerebral ischemia in the rat brain

Transient cerebral ischemia results in an increase in the tyrosine phosphor ylation of proteins associated with postsynaptic densities (PSDs). The auth ors investigated the possible mechanisms behind this increase by analyzing isolated PSDs for protein tyrosine kinase activity and for the presence of specific tyrosine kinases. Transient (15 minutes) global ischemia was produ ced in adult rats by four-vessel occlusion, and PSDs were isolated immediat ely after ischemia or after 20 minutes or 6 hours of reperfusion. Tyrosine phosphorylation of several PSD proteins, including the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B, was enhanced relative to shams aft er 20 minutes of reperfusion and underwent a further increase between 20 mi nutes and 6 hours. The ability of intrinsic PSD tyrosine kinase to phosphor ylate PSD proteins, including the NMDA receptor, increased threefold after ischemia. Whereas PSD-associated proline-rich tyrosine kinase 2 (PYK2) and gp145TrkB were elevated immediately after the ischemic event, increases in Src and Fyn were not apparent until 6 hours of reperfusion. The level of PS D-associated pp125FAK decreased after ischemia. The results demonstrate tha t ischemia results in selective changes in the association of protein tyros ine kinases with the PSD which may account for ischemia-induced increases i n the tyrosine phosphorylation of PSD proteins.