Species differences in fodrin proteolysis in the ischemic brain

✍ Scribed by Kazuo Kitagawa; Masayasu Matsumoto; Takaomi C. Saido; Toshiho Ohtsuki; Keisuke Kuwabara; Yoshiki Yagita; Takuma Mabuchi; Takehiko Yanagihara; Masatsugu Hori

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 241 KB
• Volume: 55
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19990301)55:5<643::aid-jnr11>3.0.co;2-v

✦ Synopsis

There has been growing evidence that the breakdown of cytoskeletal proteins is an important biochemical change leading to ischemic neuronal death. In the present study, we investigated species differences in the susceptibility of fodrin to calpain activation induced by cerebral ischemia in gerbils, rats, and mice. In vivo fodrin proteolysis and degradation of microtubule-associated protein 2 after complete ischemia occurred more rapidly in the hippocampus and cerebral cortex of the gerbil brain than in the corresponding area of the rat and mouse brain. The N-methyl-Daspartate (NMDA) receptor antagonist MK-801 injected intraperitoneally before ischemia did not diminish fodrin degradation in the gerbil hippocampus. In vivo fodrin proteolysis was inhibited at 33°°°°C and enhanced at 41°°°°C compared with proteolysis at 37°°°°C during ischemia. However, in vitro fodrin proteolysis after addition of Ca 2؉ into the crude membrane fraction did not show any differences among three species. Although it is highly unlikely that the difference in the sensitivity of NMDA receptor or the sensitivity of calpain activation to calcium was the crucial determinant of susceptibility of fodrin degradation in the gerbil brain, the present study clearly demonstrated that fodrin in the gerbil brain was more susceptible to calpain activation induced by ischemia than that in the rat and mouse brains. Enhanced proteolysis may be one of the reasons neurons in the gerbil brain are highly vulnerable to ischemia. J.