Changes and mechanisms of protein-tyrosine kinase and protein-tyrosine phosphatase activities after brain ischemia/reperfusion.
OBJECTIVE
To study the changes and mechanisms of protein-tyrosine kinase (PTK) and protein-tyrosine phosphatase (PTP) activities in the hippocamal synaptosome following cerebral ischemia/reperfusion (I/R) in gerbil.


METHODS
Transient (15 min) global ischemia was produced by bilateral carotid artery occlusion. Total PTK and PTP activities were measured by [r-32P] incorporation and colorimetric analysis, respectively. Src and proline-rich tyrosine kinase2 (PYK2) activities were measured by immunoprecipitation and [r-32P] incorporation.


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 increase in Src activity, but not PYK2 activity. The increase in Src activity had no relation to the expression of Src protein. Administration of ketamine (KT) or nifedipine (ND) 20 min before ischemia caused a decrease in total PTK and Src activities, and no change in the PYK2 and PTP activities.


CONCLUSIONS
The increase in PTK activity caused by I/R 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 channel (L-type VGCC). In other words, the increase in total PTK and Src activities induced by I/R may be mediated via NR and L-type VGCC. The PTP activity did not change during I/R.
Pei
L
L
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
Li
Y
Y
Yan
J Z
JZ
Zhang
G Y
GY
Cui
Z C
ZC
Zhu
Z M
ZM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology*; D002546:Ischemic Attack, Transient / Q000150:complications; D007649:Ketamine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000201:enzymology* / Q000209:etiology; D013574:Synaptosomes / Q000201:enzymology
D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D009543:Nifedipine