Ms. Kindy, INHIBITION OF TYROSINE PHOSPHORYLATION PREVENTS DELAYED NEURONAL DEATH FOLLOWING CEREBRAL-ISCHEMIA, Journal of cerebral blood flow and metabolism, 13(3), 1993, pp. 372-377
Protein tyrosine phosphorylation plays an important role in the regula
tion of neuronal function. We examined the effects of inhibition of ty
rosine phosphorylation on ischemic neuronal damage in the CA1 region o
f the hippocampus. In the gerbil hippocampus, genistein and lavendusti
n A, tyrosine kinase inhibitors, were administered 30 min before initi
ation of 5-min ischemia and reperfusion. Both genistein and lavendusti
n A blocked tyrosine phosphorylation and prevented delayed neuronal de
ath (DND). However, genistin, an inactive analogue of genistein, did n
ot block DND. Genistein was dose-dependent in the inhibition of DND af
ter ischemia and reperfusion. Administration of genistein 5 to 10 min
after ischemia and reperfusion was ineffective in blocking DND in the
CA1 region of the hippocampus. The tyrosine kinase inhibitors selectiv
ely blocked the phosphorylation of microtubule-associated protein (MAP
)-2 kinase following ischemia and reperfusion injury. These results su
ggest that tyrosine phosphorylation in the ischemic brain is important
for neuronal injury and that MAP-2 kinase may play a role in the onse
t of delayed neuronal death.