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)

Neuronal plasticity and its development were investigated at pyramidal neurons in the cortical slices of rats. The threshold and probability of firing spikes were measured by using whole-cell recording to assess neuronal excitability. Postsynaptic high frequency activity (HFA) at the pyramidal neurons, evoked by 20 trains (250-ms interval) of five depolarization-pulses (1 ms) at 100 Hz, persistently lowered the threshold and increased the probability of firing spikes. After long-term enhancement of neuronal excitability by HFA was stable, another HFA induced further enhancement. Infusing 1 mM 1,2-bis(2-aminophenoxy)-ethane-N, N,N',N'-tetraacetic acid or 100 microM CaMKII(281-301) into the recording neurons prevented HFA-induced long-term enhancement of neuronal excitability. The infusion of 40 microM calcineurin autoinhibitory peptide enhanced neuronal excitability, which occluded HFA effect. HFA-induced long-term enhancement of intrinsic excitability expressed at most pyramidal neurons after postnatal day (PND) 14, but not at those before PND 9. Our results show a new type of neuronal plasticity induced by physiological activity at cortical neurons, which requires calcium-dependent protein phosphorylation and develops during postnatal period. An upregulation of intrinsic excitability at cortical neurons facilitates their activity and broadens signal codes; consequently, their computational ability is upgraded.
 ...
PMID:Calcium signal-dependent plasticity of neuronal excitability developed postnatally. 1538 30

Previously we have demonstrated that in utero hypoxia results in increased nuclear Ca(2+)-influx and increased CaM kinase IV activity in neuronal nuclei of the guinea pig fetus. The present study tests the hypothesis that maternal treatment with magnesium sulfate (MgSO(4)) following in utero hypoxia will attenuate the hypoxia-induced increase in Ca(2+)-influx and CaM kinase IV activity in neuronal nuclei of the fetal guinea pig brain during recovery. Pregnant guinea pigs at 60 days of gestation were divided into four groups: normoxic (Nx=5), hypoxic (Hx, n=4), untreated post-hypoxic 24h recovery (Rec, n=8) and Mg(2+)-treated post-hypoxic 24h recovery (Mg(2+)-Rec, n=8). Maternal hypoxia was induced by decreasing FiO(2) to 8% for 1h. Recovery groups received either saline or 300 mg/kg MgSO(4) (i.p.) followed by 100mg/kg/h i.p. for 4h. Fetal cerebral tissue hypoxia was documented by ATP and phosphcreatine (PCr) levels. Neuronal nuclei were isolated and nuclear Ca(2+)-influx as well as CaM kinase activity was determined. Nuclear Ca(2+) influx (pmol/mg protein) was 4.84+/-0.83 in Nx, 12.50+/-2.97 (p<0.05) in Hx, 7.83+/-1.78 in Rec group (p<0.05 versus Nx and Hx) and 5.02+/-1.77 in Mg(2+)-Rec group (p<0.05 versus Rec group, p<0.05 versus Hx, p=NS versus Nx). CaM kinase IV activity (pmol/mg protein/min) was 1197+/-62 in Nx, 2524+/-132 (p<0.05 versus Nx) in Hx, 1830+/-141 (p<0.05 versus Nx and Hx) in Rec and 1938+/-118 in Mg(2+)-Rec group (p<0.05 versus Hx and Nx, p=n.s. versus Rec). The data show that MgSO(4) administration following in utero hypoxia prevents hypoxia-induced increase in neuronal nuclear Ca(2+)-influx but has no effect on CaM kinase activity in the guinea pig fetus during recovery. We conclude that post-hypoxic administration of Mg(2+) prevents hypoxia-induced modification of neuronal nuclear membrane function.
 ...
PMID:Effect of post-hypoxic MgSO(4) administration in utero on Ca(2+)-influx and Ca(2+)/calmodulin kinase IV activity in cortical neuronal nuclei. 1600 37

Much has been learned about the activity-dependent synaptic modifications that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. A good candidate for the storage mechanism is Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). CaM kinase II is one of the most prominent protein kinases, present in essentially every tissue but most concentrated in brain. Although it has been about a quarter of a century since the finding, CaM kinase II has been of the major interest in the region of brain science. It plays a multifunctional role in many intracellular events, and the expression of the enzyme is carefully regulated in brain regions and during brain development. Neuronal CaM kinase II regulates important neuronal functions, including neurotransmitter synthesis, neurotransmitter release, modulation of ion channel activity, cellular transport, cell morphology and neurite extension, synaptic plasticity, learning and memory, and gene expression. Studies concerning this kinase have provided insight into the molecular basis of nerve functions, especially learning and memory, and indicate one direction for studies in the field of neuroscience. This review presents the molecular structure, properties and functions of CaM kinase II, as a major component of neurons, based mainly developed on findings made in our laboratory.
 ...
PMID:Neuronal Ca2+/calmodulin-dependent protein kinase II--discovery, progress in a quarter of a century, and perspective: implication for learning and memory. 1607 72

It remains poorly understood as to how newly synthesized proteins that are required to act at specific synapses are translocated into only selected subsets of potentiated dendritic spines. Here, we report that F-actin, a major component of the skeletal structure of dendritic spines, may contribute to the regulation of synaptic specificity of protein translocation. We found that the stabilization of F-actin blocked the translocation of GFP-CaMKII and inhibited the diffusion of 3-kDa dextran into spines (in 2-3 weeks cultures). Neuronal activation in hippocampal slices and cultured neurons led to an increase in the activation (decrease in the phosphorylation) of the actin depolymerization factor, cofilin, and a decrease in F-actin. Furthermore, the induction of long-term potentiation by tetanic stimulation induced local transient depolymerization of F-actin both in vivo and in hippocampal slices (8-10 weeks), and this local F-actin depolymerization was blocked by APV, a N-methyl-D-aspartate (NMDA) receptor antagonist. These results suggest that F-actin may play a role in synaptic specificity by allowing protein translocation into only potentiated spines, gated through its depolymerization, which is probably triggered by the activation of NMDA receptors.
 ...
PMID:Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines. 1636 66

The phytoplankton-derived neurotoxin, domoic acid (DOM), frequently causes poisoning of marine animals and poses an increasing threat to public health through contamination of seafood. In this study, we used stereotactic microinjection technique to administer varying amounts of DOM into the hippocampal CA1 region in order to examine potential histopathological changes after injection of sub-lethal concentrations to CA1 pyramidal neurons. Gross anatomical abnormalities in CA1 were observed at above 10 microM DOM (3 pmol in 0.3 microl saline). At 1mM concentration, DOM produces both ipsilateral and contralateral neuronal cell death in CA1, CA3 as well as dentate gyrus subfields. Animal behavioral changes after microinjection were similar to those observed by previous studies through systemic DOM injection. Neuronal degeneration was paralleled by reduced glutamate receptor (NR1, GluR1 and GluR6/7) immunolabeling throughout the whole hippocampal formation. Pre-injection of the AMPA/KA receptor antagonist NBQX (10 microM, 0.3 microl) blocked 1mM DOM-induced neuronal degeneration as well as behavioral symptoms. At concentrations lower than 10 microM, no histopathological changes were observed microscopically, nor were the levels of immunostaining of NR1, GluR1, GluR6/7 different. However, increased immunolabeling of autophosphorylated calcium-calmodulin-dependent kinase II (CaMKII, p-Thr286) and phosphorylated cAMP response element binding protein (CREB, p-Ser133) were observed at 24 h post-injection, suggesting that altered intracellular signal transduction mediated by GluRs might be an adaptive cellular protective mechanism against DOM-induced neurotoxicity.
 ...
PMID:Histopathological and molecular changes produced by hippocampal microinjection of domoic acid. 1652 7

In neurons, the interaction of laminin with its receptor, beta1 integrin, is accompanied by an increase in cytosolic Ca2+. Neuronal behavior is influenced by CaMK-II, the type II Ca2+/calmodulin-dependent protein kinase, which is enriched in axons of mouse embryonic neurons. In this study, we sought to determine whether CaMK-II is activated by laminin, and if so, how CaMK-II influences axonal growth and stability. Axons grew up to 200 microm within 1 day of plating P19 embryoid bodies on laminin-1 (EHS laminin). Activated CaMK-II was found enriched along the axon and in the growth cone as detected using a phospho-Thr(287) specific CaMK-II antibody. beta1 integrin was found in a similar pattern along the axon and in the growth cone. Direct inhibition of CaMK-II in 1-day-old neurons immediately froze growth cone dynamics, disorganized F-actin and ultimately led to axon retraction. Collapsed axonal remnants exhibited diminished phospho-CaMK-II levels. Treatment of 1-day neurons with a beta1 integrin-blocking antibody (CD29) also reduced axon length and phospho-CaMK-II levels and, like CaMK-II inhibitors, decreased CaMK-II activation. Among several CaMK-II variants detected in these cultures, the 52-kDa delta variant preferentially associated with actin and beta 3 tubulin as determined by reciprocal immunoprecipitation. Our findings indicate that persistent activation of delta CaMK-II by laminin stabilizes nascent embryonic axons through its influence on the actin cytoskeleton.
 ...
PMID:Laminin activates CaMK-II to stabilize nascent embryonic axons. 1669 36

Members of the Wnt signaling family are important mediators of numerous developmental events, including activity-dependent dendrite development, but the pathways regulating expression and secretion of Wnt in response to neuronal activity are poorly defined. Here, we identify an NMDA receptor-mediated, Ca2+-dependent signaling pathway that couples neuronal activity to dendritic arborization through enhanced Wnt synthesis and secretion. Activity-dependent dendritic outgrowth and branching in cultured hippocampal neurons and slices is mediated through activation by CaM-dependent protein kinase kinase (CaMKK) of the membrane-associated gamma isoform of CaMKI. Downstream effectors of CaMKI include the MAP-kinase pathway of Ras/MEK/ERK and the transcription factor CREB. A serial analysis of chromatin occupancy screen identified Wnt-2 as an activity-dependent CREB-responsive gene. Neuronal activity enhances CREB-dependent transcription of Wnt-2, and expression of Wnt-2 stimulates dendritic arborization. This novel signaling pathway contributes to dynamic remodeling of the dendritic architecture in response to neuronal activity during development.
 ...
PMID:Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. 1677 62

Neuronal death is directly implicated in the pathogenesis of neurodegenerative diseases (NDDs). NDDs cannot be cured because the mechanisms underlying neuronal death are too complicated to be therapeutically suppressed. Neuroprotective factors, such as neurotrophins, certain growth factors, neurotrophic cytokines, and short neuroprotective peptides, support neuronal survival in both physiological and pathological conditions, suggesting that these factors may be good drug candidates for NDDs. We recently generated a novel neuroprotective peptide named Colivelin by attaching activity-dependent neurotrophic factor (ADNF) to the N-terminus of a potent Humanin derivative, AGA-(C8R)HNG17. HN was originally identified from an Alzheimer's disease (AD) brain as an endogenous neuroprotective peptide that suppresses ADrelevant toxicity. Colivelin protects neurons from death relevant to NDDs by activating two independent prosurvival signals: an ADNF-mediated Ca2+/calmodulin-dependent protein kinase IV pathway and an HN-mediated STAT3 pathway. The neuroprotective effect of Colivelin provides novel insights into therapy for NDDs.
 ...
PMID:Neuroprotection against neurodegenerative diseases: development of a novel hybrid neuroprotective peptide Colivelin. 1751 6

In the central nervous system (CNS), the synapse is a specialized junctional complex by which axons and dendrites emerging from different neuron intercommunicates. Changes in the efficiency of synaptic transmission are important for a number of aspects of neural function. Much has been learned about the activity-dependent synaptic modifications that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. Thus, it is important to find and characterize "memory molecules," and "memory apparatus or memory forming apparatus." A good candidate for the storage mechanism is Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II). CaM kinase II is one of the most prominent protein kinases, present in essentially every tissue but most concentrated in the brain. Neuronal CaM kinase II regulates important neuronal functions, including neurotransmitter synthesis, neurotransmitter release, modulation of ion channel activity, cellular transport, cell morphology and neurite extension, synaptic plasticity, learning and memory, and gene expression. Studies concerning this kinase open a door of the molecular basis of nerve function, especially learning and memory, and indicate one direction for the studies in the field of neuroscience. This review presents molecular structure, properties and functions of CaM kinase II, as a major component of neuron, which are mainly developed in our laboratory.
 ...
PMID:[Molecular mechanism of learning and memory based on the research for Ca2+/calmodulin-dependent protein kinase II]. 1766 69

Neuronal activity augments maturation of mushroom-shaped spines to form excitatory synapses, thereby strengthening synaptic transmission. We have delineated a Ca(2+)-signaling pathway downstream of the NMDA receptor that stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hippocampal neurons. CaMKK and CaMKI form a multiprotein signaling complex with the guanine nucleotide exchange factor (GEF) betaPIX and GIT1 that is localized in spines. CaMKI-mediated phosphorylation of Ser516 in betaPIX enhances its GEF activity, resulting in activation of Rac1, an established enhancer of spinogenesis. Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-negative (dn) constructs and siRNAs, as well as expression of the betaPIX Ser516Ala mutant, decreases spine formation and mEPSC frequency. Constitutively-active Pak1, a downstream effector of Rac1, rescues spine inhibition by dnCaMKI or betaPIX S516A. This activity-dependent signaling pathway can promote synapse formation during neuronal development and in structural plasticity.
 ...
PMID:Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. 1818 58


<< Previous 1 2 3 4 Next >>