Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain.
The effects of selective inhibition of cathepsins B and L on postischemic protein alterations in the brain were investigated in a rat model of middle cerebral artery occlusion (MCAO). Cathepsin B activity increased predominantly in the subcortical region of the ischemic hemisphere where the levels of collapsing mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock protein, protein disulfide isomerase A3 and albumin, were found to be significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN(2), cysteine protease inhibitor 1 (CP-1), reduced infarct volume, neurological deficits and cathepsin B activity as well as the amount of heat shock proteins and albumin found in the brain. Our data strongly suggests that the decrease in heat shock protein levels and the significant reduction of serum albumin leakage into the brain following acute treatment with CP-1 is indicative of less secondary ischemic damage, which ultimately, is related to less cerebral tissue loss and improved neurological recovery of the animals.
Department of Pathology, Henry Ford Hospital, 1 Ford Place, 5D, Detroit, MI 48202, USA.
John
J
Anagli
Kadija
K
Abounit
Paul
P
Stemmer
Yuxia
Y
Han
Lisa
L
Allred
Shantel
S
Weinsheimer
Ashkhen
A
Movsisyan
Donald
D
Seyfried
D000222:Adaptation, Physiological; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat