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

Rat parathyroid hormone (PTH) stimulates cAMP-dependent protein kinase and protein kinase C activity in the kidney. However, PTH increases intracellular Calcium in primary cultures of proximal tubular cells. We have investigated the possibility that PTH also stimulates Calcium/calmodulin-dependent protein kinase II (CaM kinase II). We have employed the tandem chromatographic column method, using synthetic peptide as a substrate, to measure the renal CaM kinase II activity. PTH (250 nM) stimulated CaM kinase II activity by about 50% after 15 sec., and activity returned to baseline by 2 min. Calmodulin antagonists significantly impaired the stimulatory action of PTH whereas basal levels of CaM kinase II activity were relatively unaffected. This study demonstrates that PTH does activate CaM kinase II in renal tissue, and suggests another pathway for the actions of PTH in the kidney.
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PMID:Effect of parathyroid hormone on rat renal calcium/calmodulin-dependent protein kinase II. 134 39

Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is composed of two distinct but related subunits, alpha and beta, in various ratios. To investigate the physiological significance of this variation, we have studied the effect of autophosphorylation of CaM kinase II isoforms purified from forebrain and cerebellum on the activity, and analyzed their endogenous protein substrates. Autophosphorylation of two kinases resulted in the appearance of Ca2(+)-independent activity and the substrate specificity of the Ca2(+)-independent form differed from that of the Ca2(+)-dependent, non-phosphorylated form of the enzyme. Increased phosphorylation of two kinases resulted in a decrease in the enzyme activity. The decrease in the enzyme activity of forebrain CaM kinase II was larger than that of cerebellar kinase. Phosphorylated forms of two kinases were less stable than the non-phosphorylated forms, and the phosphorylated form of forebrain kinase was less stable than that of cerebellar kinase. Many endogenous protein substrates of respective CaM kinase II were found in both soluble and particulate fractions of forebrain and cerebellum using gel electrophoresis. Although the major protein substrates of CaM kinase II were almost the same in forebrain and cerebellum, some of the endogenous protein substrates of respective CaM kinase II were found to be different in both soluble and particulate fractions of forebrain and cerebellum.
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PMID:Characterization of calcium/calmodulin-dependent protein kinase II isoforms from forebrain and cerebellum. 164 49

Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a prominent enzyme in mammalian brain capable of phosphorylating a variety of substrate proteins. In the present investigation, the subcellular and regional distribution of CaM kinase II has been studied by light and electron microscopic immunocytochemistry using an antibody that recognizes the Mr 50,000 and 60,000/58,000 subunits of the enzyme. Light microscopy demonstrates strong immunoreactivity in neuronal somata and dendrites and weak immunoreactivity in axons. Electron microscopy, in addition to confirming light microscopic observations, reveals moderate immunoreactivity in spines and weak immunoreactivity in nerve terminals. An accumulation of immunoreaction product is also present on postsynaptic densities. The presence of CaM kinase II in diverse structures throughout the neuron supports the view that this enzyme may be involved in mediating a variety of calcium-dependent physiological processes. CaM kinase II immunoreactivity is present in neurons throughout the brain, but a marked regional variation in the strength of the immunoreactivity exists. Overall, there is a gradient of staining intensity with the strongest immunoreactivity in the telencephalon and the weakest in the myelencephalon. The most heavily labeled regions of the telencephalon are the hippocampal formation, lateral septum, cortical regions, neostriatum, and amygdaloid complex.
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PMID:Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain. 659 Dec 8

Alterations in protein phosphorylation may be important in the pathogenesis of Alzheimer's disease and recent observations suggest that a subset of protein kinase pathways may be selectively altered. Calcium/calmodulin-dependent protein kinase II CaM kinase II) is the most abundant protein kinase in the brain and is believed to play an important role in the regulation of synaptic transmission, long-term potentiation and other forms of neuronal plasticity. We have now evaluated brains of individuals with Alzheimer's disease for changes in the distribution and density of immunoreactivity for the alpha subunit of CaM kinase II. CaM kinase II immunoreactivity was found in cytoarchitectural areas and neurons vulnerable to the formation of neurofibrillary angles and senile plaques. Over 80% of neurons bearing neurofibrillary tangles expressed CaM kinase II. Loss of CaM kinase II immunoreactivity was found in CA1, commensurate with neuronal loss in this area. Remaining CA1 neurons, however, had preserved CaM kinase II immunoreactivity. Preservation in the distribution and density of CaM kinase II immunoreactivity was observed in other hippocampal regions and in a multimodal association area, area 20. These results suggest CaM kinase II expression in the Alzheimer's disease brain is unaltered despite marked neuropathological changes.
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PMID:Calcium/calmodulin-dependent protein kinase II immunostaining is preserved in Alzheimer's disease hippocampal neurons. 782 Jun 30

Calcium/calmodulin-dependent protein kinase II (CaM kinase II) has been proposed to play a key role in glucose stimulated insulin secretion. Using the rapid amplification of cDNA ends technique we amplified the 3' end of the CaM kinase II gamma gene from human islet RNA. A novel cDNA was detected composed of 5' sequence from the human CaM kinase II gamma gene joined to the 3' end of the human signal recognition particle 72 (SRP72) gene. We predict that this mRNA species will code for a truncated form of CaM kinase II, designated gammaSRP, comprising the entire catalytic and regulatory domains of the protein and with a predicted molecular weight of 37 kDa. We mapped the human SRP72 gene to chromosome 18 and, as the CaM kinase II gamma gene was previously mapped to human chromosome 10q22, we suggest this novel cDNA may have resulted from trans-splicing.
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PMID:A truncated isoform of Ca2+/calmodulin-dependent protein kinase II expressed in human islets of Langerhans may result from trans-splicing. 922 93

Calcium/calmodulin-dependent protein kinase II (CaM kinase) activity is inhibited in cultured hippocampal cells following direct application of glutamate. The goal of the present study was to determine if hippocampal regions that undergo delayed cell death following glutamate microinfusion would exhibit changes in CaM kinase immunoreactivity. Gerbils received bilateral intra-hippocampal infusions of L-glutamate (34 microg/microl), or control treatments of D-glutamate or saline. Animals were sacrificed at 12 or 24 hr to assess cell loss and determine changes in CaM kinase-like immunoreactivity. Hippocampi of gerbils euthanized 12 hr following L-glutamate, or 24 hr following D-glutamate, did not exhibit cell death in the hippocampal CA1 region. Animals injected with L-glutamate and sacrificed 24 hr after infusion had extensive cell damage that was restricted to the hippocampal CA1 region. CaM kinase-like immunoreactivity was absent in the hippocampal CA1 region of all L-glutamate treated animals sacrificed at 12 hr. In these same sections, CaM kinase immunoreactivity was evident in the subiculum, CA2 and CA3 regions. Reduction in CaM kinase immunoreactivity following L-glutamate were also observed using Western analysis. The results confirm and extend the findings of earlier cell culture studies by demonstrating a reduction in CaM kinase immunoreactivity that occurred prior to cell death.
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PMID:In vivo glutamate neurotoxicity is associated with reductions in calcium/calmodulin-dependent protein kinase II immunoreactivity. 1021 73

Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal (CaMKII-alphaB) is altered in retinal neurons exposed to N-methyl-D-aspartate (NMDA). AIP (myristoylated autocamtide-2-related inhibitory peptide), a specific inhibitor of CaMKII provides neuroprotection against NMDA-mediated neurotoxicity. In this study, gene-arrays were used to investigate which apoptosis-associated genes are altered after exposure to NMDA. The data indicate an increased expression (2-7-fold) of five such genes encoding proteins that could be involved in NMDA induced cell death. The up-regulated genes are: FasL; GADD45; GADD153; Nur77 and TNF-R1. Treatment with AIP blocked their altered expression. The results suggest that multiples genes are involved in NMDA-induced excitotoxicity and that AIP, a specific inhibitor for CaMKII, regulates the expression of these apoptosis-associated genes in the retina.
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PMID:Characterization of apoptosis-genes associated with NMDA mediated cell death in the adult rat retina. 1145 90

A prominent cognitive impairment after traumatic brain injury (TBI) is hippocampal-dependent memory loss. Although the histopathologic changes in the brain are well documented after TBI, the underlying biochemical mechanisms that contribute to memory loss have yet to be thoroughly delineated. Thus, we determined if calcium/calmodulin-dependent protein kinases (CaMKs), known to be necessary for the formation of hippocampal-dependent memories, are regulated after TBI. Sprague-Dawley rats underwent moderate parasagittal fluid-percussion brain injury on the right side of the parietal cortex. The ipsilateral hippocampus and parietal cortex were Western blotted for phosphorylated, activated alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII), CaMKIV, and CaMKI. alpha-Calcium/calmodulin-dependent protein kinase II was activated in membrane subcellular fractions from the hippocampus and parietal cortex 30 mins after TBI. CaMKI and CaMKIV were activated in a more delayed manner, increasing in phosphorylation 1 h after TBI. The increase in activated alpha-CaMKII in membrane fractions was accompanied by a decrease in cytosolic total alpha-CaMKII, suggesting redistribution to the membrane. Using confocal microscopy, we observed that alpha-CaMKII was activated within hippocampal neurons of the dentate gyrus, CA3, and CA1 regions. Two downstream substrates of alpha-CaMKII, the AMPA-type glutamate receptor GluR1, and cytoplasmic polyadenylation element-binding protein, concomitantly increased in phosphorylation in the hippocampus and cortex 1 h after TBI. These results demonstrate that several of the biochemical cascades that subserve memory formation are activated unselectively in neurons after TBI. As memory formation requires activation of CaMKII signaling pathways at specific neuronal synapses, unselective activation of CaMKII signaling in all synapses may disrupt the machinery for memory formation, resulting in memory loss after TBI.
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PMID:Activation of calcium/calmodulin-dependent protein kinases after traumatic brain injury. 1657 77

Calcium/calmodulin-dependent protein kinase II-alpha (CaMKII-alpha) has been implicated in a number of receptor mediated events in neurons. Pharmacological blockade of CaMKII-alpha has been shown to prevent phosphorylation of NMDA-R2A and R2B receptor subunits, suggesting that this enzyme may be linked to receptor trafficking of glutamate receptors and serve as a regulatory protein for neuronal cell death. In the retina, inhibition of CaMKII-alpha has been reported to be neuroprotective against NMDA-induced cell death by preventing the activation of the caspase-3 dependent pathway. However, the effects of CaMKII-alpha blockade on the caspase-3 independent, PARP-1 dependent and the non-programmed cell death pathways have not previously been investigated. In the present study, blockade of CaMKII-alpha with the highly specific antagonist myristoylated autocamtide-2-related inhibitory peptide (AIP) was used in a rat in vivo model of retinal toxicity to compare the effects of on NMDA-induced caspase-3-dependent, PARP-1 dependent and the non-programmed (necrosis) cell death pathways. Results confirmed that AIP fully attenuates caspase-3 activation for at least 8 h following NMDA insult and also significantly improves retinal ganglion cell survival. However, this blockade had little effect on reducing the loss of plasma membrane selectivity (LPMS, e.g. necrosis) in cells located in the ganglion cell and inner nuclear layers and did not alter NMDA-induced PARP-1 hyperactivation, or prevent TUNEL labeling following a moderate NMDA-insult. These findings support a specific role for CaMKII-alpha in mediating the caspase-3 dependent cell death pathway and provide evidence that it is not directly linked to the signaling of either the PARP-1 dependent or the non-programmed cell death pathways.
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PMID:Selective blockade of CaMKII-alpha inhibits NMDA-induced caspase-3-dependent cell death but does not arrest PARP-1 activation or loss of plasma membrane selectivity in rat retinal neurons. 1913 86