Changes of Ca2+/calmodulin-dependent protein kinase-II after transient ischemia in gerbil hippocampus.
Transient cerebral ischemia induces, besides delayed neurodegeneration in selected brain structures, a number of early responses which may mediate ischemic injury/repair processes. Here we report that 5 min exposure to cerebral ischemia in gerbils induces a rapid inhibition and subsequent translocation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). These changes were partially reversible during a 24 h post-ischemic recovery. Concomitantly the total amount of the enzyme protein, as revealed by Western blotting (alpha-subunit specific), remained stable. This is consistent with our previous hypothesis, that the mechanism of ischemic CaMKII down-regulation involves a reversible posttranslational modification-(auto)phosphorylation, rather than the degradation of enzyme protein. The effectiveness of known modulators of post-ischemic outcome in counteracting CaMKII inhibition was tested. Three of these drugs, namely dizocilpine (MK-801), N-nitro-L-arginine methyl ester (L-NAME) and ginkgolide (BN52021), all significantly attenuated the enzyme response to ischemia, whereas an obvious diversity in the time-course of their actions implicates different mechanisms involved.
Zalewska
T
T
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Zabłocka
B
B
Domańska-Janik
K
K
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008297:Male
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases