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)

In this review the current knowledge of the anatomy, development and plasticity of the rodent corticospinal tract is summarised. Recent technical advancements, especially in neuronal tracing methods, have provided much new data concerning the anatomy of the corticospinal tract. The rodent corticospinal axons project to the subcortical nuclei via collateral branches. These collateral branches of corticospinal axons are formed by delayed interstitial budding during early postnatal periods. Corticospinal neurons are generated in the ventricular zone during a short time lag, migrate into the cortical plate, and settle in layer V of the cerebral cortex. The migration of corticospinal neurons is experimentally deranged by prenatal exposure to alcohol or genetically affected by the reeler genetic locus (rl), resulting in generation of ectopic corticospinal neurons. Such experimentally or genetically induced ectopic corticospinal neurons are a good model for examining whether target recognition and path finding are affected by the intracortical position of corticospinal neurons. Some chemical molecules (e.g. L1 and B-50/GAP43) are transiently expressed in the corticospinal tract during the perinatal period, while others (e.g. protein kinase C gamma subspecies and alpha CaM kinase II) are permanently expressed in the adult corticospinal tract. The only chemical marker specific for layer V corticofugal neurons is an antibody to a soluble protein, protein 35. Since the corticospinal tract in the rodent is an easily identified group of fibers situated in the most ventral portion of the dorsal funiculus of the spinal cord and exhibits considerable postnatal development, it has often been utilized in the neurological studies on plasticity and regenerative capacity of the lesioned central nervous system. Recently, it has been clarified that growing corticospinal fibers have the ability to penetrate and traverse across the lesion sites under certain special conditions.
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PMID:Anatomy, development and lesion-induced plasticity of rodent corticospinal tract. 756 96

The levels of protein kinase C-gamma (PKC-gamma ) and the calcium/calmodulin-dependent kinase II-alpha (CaMKII-alpha) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCgamma decreased in S3 without any significant increases in P2 and P3. Total PKC-gamma also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-alpha levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-alpha during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-alpha are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-alpha translocation may prove beneficial against ischemic cell death.
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PMID:Protein kinase C-gamma and calcium/calmodulin-dependent protein kinase II-alpha are persistently translocated to cell membranes of the rat brain during and after middle cerebral artery occlusion. 1468 16

Intermittent hypoxia (IH) occurs in many pathological conditions. However, very little is known about the molecular mechanisms associated with IH. Hypoxia-inducible factor 1 (HIF-1) mediates transcriptional responses to continuous hypoxia. In the present study, we investigated whether IH activates HIF-1 and, if so, which signaling pathways are involved. PC12 cells were exposed to either to 20% O2 (non-hypoxic control) or to 60 cycles consisting of 30 s at 1.5% O2, followed by 4 min at 20% O2 (IH). Western blot analysis revealed significant increases in HIF-1alpha protein in nuclear extracts of cells subjected to IH. Expression of a HIF-1-dependent reporter gene was increased 3-fold in cells subjected to IH. Although IH induced the activation of ERK1, ERK2, JNK, PKC-alpha, and PKC-gamma, inhibitors of these kinases and of phosphatidylinositol 3-kinase did not block HIF-1-mediated reporter gene expression induced by IH, indicating that signaling via these kinases was not required. In contrast, addition of the intracellular Ca2+ chelator BAPTA-AM or the Ca2+/calmodulin-dependent (CaM) kinase inhibitor KN93 blocked reporter gene activation in response to IH. CaM kinase activity was increased 5-fold in cells subjected to IH. KN 93 prevented IH-induced transactivation mediated by HIF-1alpha, and its coactivator p300, which was phosphorylated by CaM kinase II in vitro. Expression of the HIF-1-regulated gene encoding tyrosine hydroxylase was induced by IH and this effect was blocked by KN93. These observations suggest that IH induces HIF-1 transcriptional activity via a novel signaling pathway involving CaM kinase.
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PMID:Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia. 1556 87

Long-term potentiation in sympathetic ganglia (gLTP) is similar to LTP of the hippocampal area CA1 in that its expression involves similar changes in signaling molecules. We have shown previously that the stress-prone, hypertensive obese Zucker rats (OZR) expressed gLTP in sympathetic ganglia and that high blood pressure was reduced by treatment with 5-HT(3) receptor antagonists. In the present study, we present additional electrophysiological evidence for the pre-expression of gLTP in sympathetic ganglia from OZR indicated by failure of repetitive stimulation to express gLTP in isolated superior cervical ganglia (SCG) and inhibition of baseline ganglionic transmission by a 5-HT(3) receptor antagonist. We have also investigated the role of key signaling molecules in the expression of gLTP in the hypertensive OZR. Immunoblot analysis showed a significant increase in the levels of phosphorylated (P-)CaMKII and protein kinase C gamma (PKCgamma) in SCG from OZR. The ratio of P-CaMKII to the total CaMKII was markedly increased in OZR ganglia, suggesting increased phosphorylation of this molecule. Additionally, there was a significant decrease in the levels of calcineurin in ganglia. Furthermore, the neural nitric oxide synthase and hemeoxygenase II, which are essential for the expression of gLTP, were significantly elevated in OZR ganglia. The present findings confirm that ganglia from OZR have expressed gLTP and that synaptic plasticity in sympathetic ganglia may involve a molecular cascade similar to that of LTP of the brain hippocampal area CA1.
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PMID:Expression of gLTP in sympathetic ganglia of obese Zucker rats in vivo: molecular evidence. 1856 1