Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient cerebral ischemia demonstrates an increase in activated oxygen species in the brain that could lead to eventual neuronal cell death. Neuronal cells respond to oxygen free radicals through the restructuring of the cytoskeleton and membranes, mobilization of calcium and gene expression which play a role in cell injury. Ten min of bilateral carotid artery occlusion resulted in a decrease in calcium/calmodulin dependent protein kinase II (CaM kinase II) phosphorylation and activity detected in the brain immediately following ischemia and was partially restored within 24 h of reperfusion. Pretreatment of animals with an anesthetic dose of pentobarbital (40 mg/kg) resulted in partial protection of inactivation of CaM kinase II following ischemia. CaM kinase II activity was maintained following pretreatment of animals with alpha-phenyl N-tert-butyl nitrone (PBN), which traps oxygen free radicals. Infusion of superoxide dismutase or catalase prior to ischemia, blocked CaM kinase II inactivation. Blockage of calcium uptake with bepridil resulted in a marked protection of CaM kinase II inactivation. In addition, trifluoperazine, a calmodulin antagonist also diminished the inhibition of CaM kinase II phosphorylation in our model. These results suggest that ischemia and reperfusion injury results in the generation of activated oxygen and the mobilization of calcium which inactivate CaM kinase II. These results indicate that changes associated with protein kinase activity in the brain following an ischemic insult may have profound effects upon neurodegeneration and neuronal survival.
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PMID:Role of calcium in inactivation of calcium/calmodulin dependent protein kinase II after cerebral ischemia. 133 39

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.
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PMID:Changes of Ca2+/calmodulin-dependent protein kinase-II after transient ischemia in gerbil hippocampus. 878 2