Suppressive effect of E-64c on ischemic degradation of cerebral proteins following occlusion of the middle cerebral artery in rats.
Microtubule-associated protein 2 (MAP2) levels in the left cerebral hemisphere decreased significantly 3 days after occlusion of the left middle cerebral artery in rats to 29 +/- 16.3% of control levels. Since MAP2 is one of the substrates of calpain, E-64c, a synthetic calpain inhibitor, was administered at a dose of 400 mg/kg twice a day for 3 days, with the first dose being given before the production of ischemia. This depletion was significantly inhibited in vivo by E-64c (P less than 0.05) to increase MAP2 levels to 55 +/- 25.7% of control levels. E-64c had no significant effect on the ischemia-induced depletion of myelin-associated glycoprotein. Sham-operated rats were used as controls. Our results suggest that calpain is partially involved in the degradation of MAP2, and that the use of calpain inhibitors can be a useful clinical approach to cerebral ischemia.
Inuzuka
T
T
Department of Neurology, Niigata University, Japan.
Tamura
A
A
Sato
S
S
Kirino
T
T
Toyoshima
I
I
Miyatake
T
T
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D002536:Cerebral Arteries; D015151:Immunoblotting; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009185:Myelin Proteins / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein; D051381:Rats; D011919:Rats, Inbred Strains
D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; D002154:Calpain; D007930:Leucine