Stimulation of protein tyrosine phosphorylation participates in
delayed neuronal death in ischemic hippocampus.
Ohtsuki, Toshiho, Masayasu Matsumoto, Kazuo Kitagawa, Takuma Mabuchi,
Kenji Mandai, Kohji Matsushita, Keisuke Kuwabara, Masafumi Tagaya,
Satoshi Ogawa, Hirokazu Ueda, Takenobu Kamada, and Takehiko
Yanagihara.
First Department of Medicine and Department of Neurology, Osaka
University Medical School, Osaka 565, Japan
APStracts 3:0129C, 1996.
Glutamate triggers neuronal degeneration following
ischemia/reperfusion in the brain. However, the details of
intracellular signal transduction that propagate cell death remain
unknown. The present work investigated whether protein tyrosine
phosphorylation mediates neuronal death in the ischemic brain.
Transient forebrain ischemia for 5- 10 min in Mongolian gerbils or
intoxication of glutamate analog (kainic acid, 12 mg/kg) in Sprague
-Dawley rats caused neuronal death selectively in the hippocampus 2-4
days or 1 day later, respectively. Under these conditions, 160, 115,
105, 92, 85 kDa proteins showed a significant increase in tyrosyl
residue phosphorylation selectively in the hippocampus 3-12 h after
ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine
kinases, including pp60c-src, were activated without a change of
tyrosine phosphatases. Administration of radicicol, a selective
inhibitor of tyrosine kinases, attenuated stimulation of tyrosine
phosphorylation and hippocampal degeneration after ischemia or kainic
acid injection. The results suggest that protein tyrosine
phosphorylation might propagate delayed neuronal death in the mature
hippocampus through glutamate overload after ischemia/reperfusion.
Received 13 November 1995; accepted in final form 26 March 1996.
APS Manuscript Number C684-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96