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Calcium/calmodulin-dependent kinase type II

Federica Bosco, Pierluigi Valente, Marco Milanese, Alessandra Piccini, Mirko Messa, Giambattista Bonanno, Paul Lombroso, Pietro Baldelli, Fabio Benfenati, Silvia Giovedì
The striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase involved in synaptic transmission. The current hypothesis on STEP function holds that it opposes synaptic strengthening by dephosphorylating and inactivating key neuronal proteins involved in synaptic plasticity and intracellular signaling, such as the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. Although STEP has a predominant role at the post-synaptic level, it is also expressed in nerve terminals...
March 5, 2018: Molecular Neurobiology
Lennard J M Dekker, Lona Zeneyedpour, Sandor Snoeijers, Jos Joore, Sieger Leenstra, Theo M Luider
We show that parallel reaction monitoring (PRM) can be used for exact quantification of phosphorylation ratios of proteins using stable isotope labelled peptides. We have compared two different PRM approaches on a digest of a U87 cell culture, namely direct-PRM (tryptic digest measured by PRM without any further sample preparation) and TiO2-PRM (tryptic digest enriched with TiO2 cartridges, followed by PRM measurement); these approaches are compared for the following phosphorylation sites: Neuroblast differentiation-associated protein (AHNAK S5480-p), Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D T337-p) and Epidermal growth factor receptor (EGFR S1166-p)...
February 19, 2018: Journal of Proteome Research
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
Tyler Shugg, Derrick E Johnson, Minghai Shao, Xianyin Lai, Frank Witzmann, Theodore R Cummins, Michael Rubart-Von-der Lohe, Andy Hudmon, Brian R Overholser
BACKGROUND: Sustained β-adrenergic receptor (β-AR) stimulation causes pathophysiologic changes during heart failure (HF), including inhibition of the slow component of the delayed rectifier current, IKs. Aberrant calcium handling, including increased activation of calcium/calmodulin-dependent protein kinase II (CaMKII), contributes to arrhythmia development during HF. OBJECTIVE: To investigate CaMKII regulation of KCNQ1 (pore-forming subunit of IKs) during sustained β-AR stimulation and associated functional implications on IKs...
February 1, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Obialunanma V Ebenebe, Alison Heather, Jeffrey R Erickson
Signalling mechanisms within and between cells of the vasculature enable function and maintain homeostasis. However, a number of these mechanisms also contribute to the pathophysiology of vascular disease states. The multifunctional signalling molecule calcium/calmodulin-dependent kinase II (CaMKII) has been shown to have critical functional effects in many tissue types. For example, CaMKII is known to have a dual role in cardiac physiology and pathology. The function of CaMKII within the vasculature is incompletely understood, but emerging evidence points to potential physiological and pathological roles...
December 19, 2017: Heart, Lung & Circulation
Chinnakkaruppan Adaikkan, Elham Taha, Iliana Barrera, Orit David, Kobi Rosenblum
BACKGROUND: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear. METHODS: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
December 5, 2017: Biological Psychiatry
A E Gaydukov, O P Balezina
We investigated the involvement of calcium-dependent enzymes, protein kinase C (PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the signaling pathway triggered by the activation of presynaptic alpha7-type nicotinic acetylcholine receptors by exogenous choline, leading to downregulation of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of PKC with chelerythrine neither changed the evoked release of ACh by itself nor prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not affect synaptic activity but fully prevented the choline-induced downregulation of ACh release...
October 2017: Acta Naturae
Hugo R Arias, Olena Lykhmus, Kateryna Uspenska, Maryna Skok
In contrast to plasma membrane-expressed nicotinic acetylcholine receptors (nAChRs), mitochondrial nAChRs function in an ion-independent manner by triggering intra-mitochondrial kinases that regulate the release of cytochrome c (Cyt c), an important step in cellular apoptosis. The aim of this study is to determine the structural requirements for mitochondrial α3β4* nAChR activation by measuring the modulatory effects of two noncompetitive antagonists of these receptors, (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC], on Cyt c release from wild-type and α7-/- mice mitochondria...
December 22, 2017: Neurochemistry International
Shigeki Moriguchi, Satomi Kita, Masahiro Fukaya, Makoto Osanai, Ryo Inagaki, Yuzuru Sasaki, Hisanao Izumi, Kyoji Horie, Junji Takeda, Takashi Saito, Hiroyuki Sakagami, Takaomi C Saido, Takahiro Iwamoto, Kohji Fukunaga
Na+/Ca2+ exchangers (NCXs) are expressed primarily in the plasma membrane of most cell types, where they mediate electrogenic exchange of one Ca2+ for three Na+ ions, depending on Ca2+ and Na+ electrochemical gradients across the membrane. Three mammalian NCX isoforms (NCX1, NCX2, and NCX3) are each encoded by a distinct gene. Here, we report that NCX2 and NCX3 protein and mRNA levels are relatively reduced in hippocampal CA1 of APP23 and APP-KI mice. Likewise, NCX2+/- or NCX3+/- mice exhibited impaired hippocampal LTP and memory-related behaviors...
December 22, 2017: Neuropharmacology
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
Song Zuo, Lin-Ling Li, Yan-Fei Ruan, Le Jiang, Xin Li, Song-Nan Li, Song-Nan Wen, Rong Bai, Nian Liu, Xin Du, Jian-Zeng Dong, Chang-Sheng Ma
Aims: The arrhythmogenic mechanisms of atrial fibrillation (AF) that are induced by acute inflammation, such as postoperative AF, are not well understood. We investigated the acute effects of tumour necrosis factor-α (TNF-α) that mimic acute inflammation on Ca2+ handling in isolated atrial myocytes and its underlying mechanisms. Methods and results: Cytosol Ca2+ handling and mitochondrial reactive oxygen species (ROS) production were studied in freshly isolated atrial myocytes of wild-type mice that were exposed to TNF-α (0...
October 17, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Liyin Yu, Xingfeng Ma, Junqin Sun, Jie Tong, Liang Shi, Lijun Sun, Jianbao Zhang
Numerous studies have demonstrated that fluid shear stress (FSS) may promote the proliferation and differentiation of osteoblast cells. However, proliferation and differentiation are mutually exclusive processes and are unlikely to be promoted by FSS simultaneously. Cell proliferation and differentiation induced by FSS has rarely been reported. In order to provide an insight into this process, the present study investigated the effects of FSS on osteoblast‑like MC3T3 cells in the G0/G1 phase, the period during which the fate of a cell is determined...
December 2017: Molecular Medicine Reports
Elena A Kuklin, Stephen Alkins, Baskar Bakthavachalu, Maria C Genco, Indulekha Sudhakaran, K Vijay Raghavan, Mani Ramaswami, Leslie C Griffith
A null mutation of the Drosophila calcium/calmodulin-dependent protein kinase II gene (CaMKII) was generated using homologous recombination. Null animals survive to larval and pupal stages due to a large maternal contribution of CaMKII mRNA, which consists of a short 3'-untranslated region (UTR) form lacking regulatory elements that guide local translation. The selective loss of the long 3'UTR mRNA in CaMKII-null larvae allows us to test its role in plasticity. Development and evoked function of the larval neuromuscular junction are surprisingly normal, but the resting rate of miniature excitatory junctional potentials (mEJPs) is significantly lower in CaMKII mutants...
November 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sinai Li, Yibing Nong, Qun Gao, Jing Liu, Yan Li, Xiaoyun Cui, Jie Wan, Jinjin Lu, Mingjie Sun, Qian Wu, Xiaolu Shi, Haifeng Cui, Weihong Liu, Mingxue Zhou, Lina Li, Qian Lin
BACKGROUND: Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca(2+) current (ICa-L) in HF mice by the downregulation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). METHODS: HF mice were induced by thoracic aortic constriction (TAC)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Chung-Chuan Chou, Chien-Te Ho, Hui-Ling Lee, Yen Chu, Tzung-Hai Yen, Ming-Shien Wen, Shien-Fong Lin, Cheng-Hung Lee, Po-Cheng Chang
BACKGROUND: Diabetes mellitus is associated an increased risk of ventricular arrhythmias (VAs), but the underlying electrophysiological mechanisms are not fully explored. This study was aimed to test whether dynamic factors and Cai handling play roles in arrhythmogenesis of a diabetic animal model. METHODS: We used 26 db/db type 2 diabetes mice and 28 control mice in this study. VA inducibility was evaluated in vivo under isoflurane general anesthesia. The intracellular Ca(2+) (Cai ) and membrane voltage (Vm ) signals of the Langendorff-perfused mouse hearts were simultaneously recorded using the optical mapping technique...
August 26, 2017: Pacing and Clinical Electrophysiology: PACE
Enjie Liu, Ao-Ji Xie, Qiuzhi Zhou, Mengzhu Li, Shujuan Zhang, Shihong Li, Weijin Wang, Xiaochuan Wang, Qun Wang, Jian-Zhi Wang
Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3β(lox/lox) mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms...
July 18, 2017: Scientific Reports
Weijie Wang, Yingcong Yu, Jing Li, Lin Wang, Zhi Li, Chong Zhang, Linlin Zhen, Lianshu Ding, Gang Wang, Xiaoyang Sun, Ying Xu
Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca(2+)/calmodulin-dependent signaling in the spinal cord of mice...
August 2017: Metabolic Brain Disease
Xinyu Yang, Yu Chen, Yanda Li, Xiaomeng Ren, Yanwei Xing, Hongcai Shang
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group...
2017: BioMed Research International
Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber, Thomas Wieland, Samuel Sossalla, Johannes Backs, Joan H Brown, Lars S Maier, Ali El-Armouche
BACKGROUND: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF...
May 2017: Circulation. Heart Failure
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
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