Activities of calcineurin and phosphatase 2A in the hippocampus after transient forebrain ischemia.
We investigated the changes in the enzyme activity and immunoreactivity of calcineurin in the rat hippocampus after transient forebrain ischemia. Immediately after 20-min transient forebrain ischemia, calcineurin activity decreased to about 40% of the control in the CA1 region and to about 55% in other regions. Protein phosphatase 2A activity showed no remarkable changes. By 12 h after ischemia, calcineurin activity recovered, more in the CA1 region than in other regions. At 24 h it decreased again, but only in the CA1 region. Immunohistochemical- and immunoblot analyses showed no remarkable change in calcineurin in any region of the hippocampus within 12 h after ischemia. Thus, the activity of calcineurin is dissociated from its immunoreactivity and quantity. Several studies have suggested that unknown inhibitory factor(s) and/or reversible changes in calcineurin act to modify enzyme activity after ischemia. In contrast, phosphatase 2A activity underwent no obvious changes during the post-ischemia period we examined. This unique time course of calcineurin activity may contribute to the mechanism of ischemic neuronal injury.
D000818:Animals; D019703:Calcineurin / Q000032:analysis / Q000378:metabolism*; D018891:Dentate Gyrus / Q000098:blood supply / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005296:Ferrous Compounds / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000378:metabolism*; D016548:Prosencephalon / Q000098:blood supply / Q000201:enzymology; D054648:Protein Phosphatase 2; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D016559:Tacrolimus / Q000494:pharmacology