Autophosphorylated calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) reversibly targets to and phosphorylates N-methyl-d-aspartate receptor subunit 2B (NR2B) in cerebral ischemia and reperfusion in hippocampus of rats

Meng, Fanjie; Guo, Jun; Zhang, Quanguang; Song, Bo; Zhang, Guangyi

doi:10.1016/s0006-8993(02)04267-1

Cited by 29 publications

(20 citation statements)

References 20 publications

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“…However, a dramatic decrease in T286 phosphorylation may facilitate CaMKII cluster formation, because it has been demonstrated that when T286 is mutated to alanine (an amino acid that cannot be phosphorylated) cluster formation is enhanced and when T286 is mutated to aspartate (an amino acid that mimics phosphorylation) cluster formation is inhibited (Hudmon et al, 2005). The decrease in T286 phosphorylation that we observed may explain why Kolb et al, saw a decrease in Ca 2+ -independent activity with a similar treatment (Kolb et al, 1995), but it is at odds with several reports demonstrating an increase in T286 phosphorylation following in vivo ischemia (Meng and Zhang, 2002;Tang et al, 2004;Meng et al, 2003). However, it has also been reported that sub-lethal ischemia followed by reperfusion in rats leads to a decrease in T286 phosphorylation (Shamloo et al, 2000), so our in vitro model of ischemia may more closely mimic sub-lethal as opposed to lethal in vivo ischemia.…”

Section: Discussionmentioning

confidence: 57%

αCaMKII autophosphorylation levels differ depending on subcellular localization

et al. 2007

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Calcium/calmodulin-dependent protein kinase II (CaMKII) has important roles in many processes in the central nervous system. It is enriched at the post-synaptic density (PSD), a localization which is thought to be critical for many of its proposed neuronal functions. In order to better understand the mechanisms that regulate association of CaMKII with the PSD, we compared the levels of autophosphorylation between PSD-associated kinase and kinase in other parts of the neuron. We were surprised to find that αCaMKII in a PSD-enriched fraction prepared from recovered hippocampal CA1-minislices had a relatively low level of threonine 286 (T286) phosphorylation and a relatively high level of threonine 305 (T305) phosphorylation. Furthermore, when the minislices were subjected to a treatment that mimics ischemic conditions, there was a significant translocation of αCaMKII to the PSD-enriched fraction accompanied with a dramatic reduction in T286 phosphorylation levels throughout the neuron. These findings have important implications for our understanding of the role of autophosphorylation in the localization of CaMKII.

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Section: Discussionmentioning

confidence: 57%

αCaMKII autophosphorylation levels differ depending on subcellular localization

et al. 2007

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“…It is known that, once activated, CaMKIIα translocates to the membranes, binding to and phosphorylating NR2B (Meng et al , 2003). As indicated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

Ahmed

Dong

et al. 2016

J Mol Neurosci

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Aberrant calcium influx is a common feature following ischemic reperfusion (I/R) in transient global cerebral ischemia (GCI) and causes delayed neuronal cell death in the CA1 region of the hippocampus. Activation of calcium-calmodulin (CaM) dependent protein kinase IIα (CaMKIIα) is a key event in calcium signaling in ischemic injury. The present study examined the effects of intracerebroventricular (icv) injection of tatCN21 in ischemic rats 3 hours after GCI reperfusion. Cresyl violet and NeuN staining revealed that tatCN21 exerted neuroprotective effects against delayed neuronal cell death of hippocampal CA1 pyramidal neurons 10 days post GCI. In addition, TatCN21 administration ameliorated GCI-induced spatial memory deficits in the Barnes maze task as well as anxiety-like behaviors and spontaneous motor activity in the elevated plus maze and open field test, respectively. Mechanistic studies showed that the administration of tatCN21 decreased GCI induced phosphorylation, translocation and membrane targeting of CaMKIIα. Treatment with tatCN21 also inhibited the level of CaMKIIα-NR2B interaction and NR2B phosphorylation. Our results revealed an important role of tatCN21 in inhibiting CaMKIIα activation and its beneficial effects in neuroprotection and memory preservation in an ischemic brain injury model.

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“…We have previously found that exercise uses BDNF and the CAMKII cascade to promote changes in CREB and synapsin I expression in the hippocampus (Vaynman et al, 2003). CAMKII has been found to be localized to mitochondrial membranes (Liu and Jones, 1996) and its phosphorylation to promote its binding to the postsynaptic NMDA receptor (McNeill and Colbran, 1995;Meng et al, 2003;Leonard et al, 1999), a receptor that closely interacts with BDNF (Suen et al, 1997). As the mitochondria have privileged access to sequester NMDA-induced Ca 2ϩ loads (Wang and Thayer, 2002), mitochondrial regulation may provide local Ca 2ϩ to modulate the CAMKII pathway and possibly the convergent, BDNF-induced (Jovanovic et al, 2000) mitogen-activated protein kinase (MAPK) cascade (Platenik et al, 2000;Fig.…”

Section: Intersection Of Energy Metabolism With Bdnf Signal Transductmentioning

confidence: 99%

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity

Vaynman¹,

Ying²,

Wu³

et al. 2006

Neuroscience

146

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Abstract-Synaptic plasticity and behaviors are likely dependent on the capacity of neurons to meet the energy demands imposed by neuronal activity. We used physical activity, a paradigm intrinsically associated with energy consumption/ expenditure and cognitive enhancement, to study how energy metabolism interacts with the substrates for neuroplasticity. We found that in an area critical for learning and memory, the hippocampus, exercise modified aspects of energy metabolism by decreasing oxidative stress and increasing the levels of cytochrome c oxidase-II, a specific component of mitochondrial machinery. We infused 1,25-dihydroxyvitamin D3, a modulator of energy metabolism, directly into the hippocampus during 3 days of voluntary wheel running and measured its effects on brain-derived neurotrophic factormediated synaptic plasticity. Brain-derived neurotrophic factor is a central player for the effects of exercise on synaptic and cognitive plasticity. We found that 25-dihydroxyvitamin D3 decreased exercise-induced brain-derived neurotrophic factor but had no significant effect on neurotrophin-3 levels, thereby suggesting a level of specificity for brain-derived neurotrophic factor in the hippocampus. 25-Dihydroxyvitamin D3 injection also abolished the effects of exercise on the consummate end-products of brain-derived neurotrophic factor action, i.e. cyclic AMP response element-binding protein and synapsin I, and modulated phosphorylated calmodulin protein kinase II, a signal transduction cascade downstream to brain-derived neurotrophic factor action that is important for learning and memory. We also found that exercise significantly increased the expression of the mitochondrial uncoupling protein 2, an energy-balancing factor concerned with ATP production and free radical management. Our results reveal a fundamental mechanism by which key elements of energy metabolism may modulate the substrates of hippocampal synaptic plasticity.

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Autophosphorylated calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) reversibly targets to and phosphorylates N-methyl-d-aspartate receptor subunit 2B (NR2B) in cerebral ischemia and reperfusion in hippocampus of rats

Cited by 29 publications

References 20 publications

αCaMKII autophosphorylation levels differ depending on subcellular localization

αCaMKII autophosphorylation levels differ depending on subcellular localization

Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity

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