title: Up- and down-regulation of calpain inhibitor polypeptide, calpastatin, in postischemic hippocampus.
abstract: Based on our previous observation that transient forebrain ischemia induces calpain-catalyzed proteolysis in gerbil hippocampus in a region-specific manner, we examined the effect of ischemia on the quantity and localization of the endogenous calpain-specific inhibitor protein, calpastatin, in the tissue. Brief (5 min) forebrain ischemia followed by reperfusion induced an overall increase of calpastatin immunoreactivity in hippocampus, particularly in pyramidal cells, in 4 h as analyzed by Western blotting and immunohistochemistry. The amount of calpastatin, however, decreased to the preischemic level and lower in 24 h to 7 days due to proteolysis except in CA2 showing continuously elevated calpastatin immunoreactivity. Because calpastatin is not only a potent inhibitor but also a preferred substrate for calpain and because CA2 neurons are less vulnerable to ischemic stress than the adjacent CA1 neurons, these observations imply involvement of calpastatin in calpain regulation as a bait substrate and, possibly, in neuroprotection under ischemic conditions. Calpastatin may participate in the stress responses together with the previously known ischemia-induced stress proteins such as heat shock proteins.
authors.affiliation: Department of Molecular Biology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Japan. saido@rinshoken.or.jp
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: S
authors.initials: S
authors.lastname: Kawashima
authors.forename: E
authors.initials: E
authors.lastname: Tani
authors.forename: M
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; C033668:calpastatin