Changes and mechanisms of protein-tyrosine kinase and protein-tyrosine phosphatase activities after brain ischemia/reperfusion

AIM: To study the changes and mechanisms of protein-tyrosine kinase (PTK) a nd protein-tyrosine phosphatase (PTP) activities in the hippocamal synaptos ome following cerebral ischemia/reperfusion (I/R) in gerbil. METHODS: Trans ient (15 min) global ischemia was produced by bilateral carotid artery occl usion. Total PTK and PTP activities were measured by [r-P-32] incorporation and colorimetric analysis, respectively. Src and proline-rich tyrosine kin ase2 (PYK2) activities were measured by immunoprecipitation and [r-P-32] in corporation. RESULTS: Total PTK activity increased significantly after I/R, but the PTP activity did not change. The Src activity was much higher than PYK2 activity in sham-operated controls. I/R mainly caused a pronounced in crease in Src activity, but not PYK2 activity. The increase in Src activity had no relation to the expression of Src protein. Administration of ketami ne (KT) or nifedipine (ND) 20 min before ischemia caused a decrease in tota l PTK and Src activities, and no change in the PYK2 and PTP activities. CON CLUSION: The increase in PTK activity caused by VR may be mainly due to the increase in Src activity. This increase in Src activity has no relation to the expression of Src protein. But it is related to the activation of NMDA (N-methyl-D-aspartate) receptor (NR) and L-type voltage-gated calcium chan nel (L-type VGCC). In other words, the increase in total PTK and Src activi ties induced by I/R may be mediated via NR and L-type VGCC. The PTP activit y did not change during I/R.