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CaMKII

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https://www.readbyqxmd.com/read/29046633/activity-dependent-phosphorylation-by-camkii%C3%AE-alters-the-ca-2-affinity-of-the-multi-c2-domain-protein-otoferlin
#1
Sandra Meese, Andreia P Cepeda, Felix Gahlen, Christopher M Adams, Ralf Ficner, Anthony J Ricci, Stefan Heller, Ellen Reisinger, Meike Herget
Otoferlin is essential for fast Ca(2+)-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca(2+)/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ) as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29045723/acute-administration-of-tumour-necrosis-factor-%C3%AE-induces-spontaneous-calcium-release-via-the-reactive-oxygen-species-pathway-in-atrial-myocytes
#2
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
https://www.readbyqxmd.com/read/29038242/activity-dependent-facilitation-of-cav1-3-calcium-channels-promotes-kca3-1-activation-in-hippocampal-neurons
#3
Giriraj Sahu, Hadhimulya Asmara, Fang-Xiong Zhang, Gerald W Zamponi, Ray W Turner
CaV1 L-type calcium channels are key to regulating neuronal excitability, with the range of functional roles enhanced by interactions with calmodulin, accessory proteins, or CaMKII that modulate channel activity. In hippocampal pyramidal cells a prominent elevation of CaV1 activity is apparent in late channel openings that can last for seconds following a depolarizing stimulus train. The current study tested the hypothesis that a reported interaction between CaV1.3 channels, the scaffolding protein densin, and CaMKII could generate a facilitation of channel activity that outlasts a depolarizing stimulus...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29037982/early-effects-of-epac-depend-on-the-fine-tuning-of-the-sarcoplasmic-reticulum-ca-2-handling-in-cardiomyocytes
#4
N Lezcano, J I E Mariángelo, L Vittone, X H T Wehrens, M Said, C Mundiña-Weilenmann
In cardiac muscle, signaling through cAMP governs many fundamental cellular functions, including contractility, relaxation and automatism. cAMP cascade leads to the activation of the classic protein kinase A but also to the stimulation of the recently discovered exchange protein directly activated by cAMP (Epac). The role of Epac in the regulation of intracellular Ca(2+) homeostasis and contractility in cardiac myocytes is still matter of debate. In this study we showed that the selective Epac activator, 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (8-CPT), produced a positive inotropic effect when adult rat cardiac myocytes were stabilized at low [Ca(2+)]o (0...
October 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29034548/electroacupuncture-alleviates-chemotherapy-induced-pain-through-inhibiting-phosphorylation-of-spinal-camkii-in-rats
#5
Y Zhang, A Li, J Xin, K Ren, B M Berman, L Lao, R-X Zhang
BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0...
October 16, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29030236/long-term-aerobic-exercise-in-calsequestrin2-knockout-mice-accentuates-vagal-antagonism-during-%C3%AE-adrenergic-stimulation-which-restricts-heart-rate-acceleration-and-paradoxically-increases-abnormal-ryanodine-receptor-calcium-leak-in-ventricular-myocytes
#6
Hsiang-Ting Ho, Senthil Thambidorai, Björn C Knollmann, George E Billman, Sandor Györke, Anuradha Kalyanasundaram
BACKGROUND: Long-term aerobic exercise (EX) alters autonomic balance which may not be favorable in heart rate (HR) dependent arrhythmic diseases including Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) due to preexisting bradycardia and increased sensitivity to parasympathetic stimulation. OBJECTIVE: The purpose of this study was to determine if long-term exercise-induced autonomic adaptations modify CPVT susceptibility. METHODS: We determined exercise-induced parasympathetic effects on HR, arrhythmia incidence and intracellular sarcoplasmic reticulum (SR) Ca(2+) leak in atrial (ACM) and ventricular (VCM) cardiomyocytes, in EX Calsequestrin knockout (CASQ2(-/-)) mice, a model of CPVT...
October 10, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29024786/neurobiological-correlates-of-pain-avoidance-like-behavior-in-morphine-dependent-and-non-dependent-rats
#7
Amanda R Pahng, Rod I Paulsen, M Adrienne McGinn, Kimberly N Edwards, Scott Edwards
Repeated use of opioids can lead to the development of analgesic tolerance and dependence. Additionally, chronic opioid exposure can cause a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may drive continued or escalated use of opioids to manage worsening pain symptoms. Opioid-induced hyperalgesia has traditionally been measured in rodents via reflex-based assays, including the von Frey method. To better model the cognitive/motivational dimension of pain in a state of opioid dependence and withdrawal, we employed a recently developed non-reflex-based method for measuring pain avoidance-like behavior in animals (mechanical conflict avoidance test)...
October 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29017032/a-mechanism-coupling-systemic-energy-sensing-to-adipokine-secretion
#8
Akhila Rajan, Benjamin E Housden, Frederik Wirtz-Peitz, Laura Holderbaum, Norbert Perrimon
Adipocytes sense systemic nutrient status and systemically communicate this information by releasing adipokines. The mechanisms that couple nutritional state to adipokine release are unknown. Here, we investigated how Unpaired 2 (Upd2), a structural and functional ortholog of the primary human adipokine leptin, is released from Drosophila fat cells. We find that Golgi reassembly stacking protein (GRASP), an unconventional secretion pathway component, is required for Upd2 secretion. In nutrient-rich fat cells, GRASP clusters in close proximity to the apical side of lipid droplets (LDs)...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28992057/ca2-calmodulin-dependent-protein-kinase-ii-promotes-neurodegeneration-caused-by-tau-phosphorylated-at-ser262-356-in-a-transgenic-drosophila-model-of-tauopathy
#9
Mikiko Oka, Naoki Fujisaki, Akiko Maruko-Otake, Yosuke Ohtake, Sawako Shimizu, Taro Saito, Shin-Ichi Hisanaga, Koichi M Iijima, Kanae Ando
Abnormal deposition of the microtubule-associated protein tau is a common pathological feature of multiple neurodegenerative diseases, including Alzheimer's disease (AD), and plays critical roles in their pathogenesis. Disruption of calcium homeostasis and the downstream kinase Ca2+/calmodulin-dependent protein kinase II (CaMKII) coincides with pathological phosphorylation of tau in AD brains. However, it remains unclear whether and how dysregulation of CaMKII affects tau toxicity. Using a Drosophila model, we found that CaMKII promotes neurodegeneration caused by tau phosphorylated at the AD-associated sites Ser262/356...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28981869/overexpression-of-neuregulin-1-type-iii-confers-hippocampal-mrna-alterations-and-schizophrenia-like-behaviors-in-mice
#10
Juan C Olaya, Carrie L Heusner, Mitsuyuki Matsumoto, Duncan Sinclair, Mari A Kondo, Tim Karl, Cynthia Shannon Weickert
Neuregulin 1 (NRG1) is a schizophrenia candidate gene whose protein product is involved in neuronal migration, survival, and synaptic plasticity via production of specific isoforms. Importantly, NRG1 type III (NRG1 III) mRNA is increased in humans inheriting a schizophrenia risk haplotype for the NRG1 gene (HapICE), and NRG1 protein levels can be elevated in schizophrenia. The nature by which NRG1 type III overexpression results in schizophrenia-like behavior and brain pathology remains unclear, therefore we constructed a transgenic mouse with Nrg1 III overexpression in forebrain neurons (CamKII kinase+)...
September 8, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28981195/nhe5-deficiency-enhances-learning-and-memory-via-upregulating-bdnf-trkb-signaling-in-mice
#11
Xuejiao Chen, Xiyi Wang, Lingyun Tang, Jinjin Wang, Chunling Shen, Jianbing Liu, Shunyuan Lu, Hongxin Zhang, Ying Kuang, Jian Fei, Zhugang Wang
Nhe5, a Na(+) /H(+) exchanger, is predominantly expressed in brain tissue and is proposed to act as a negative regulator of dendritic spine growth. Up to now, its physiological function in vivo remains unclear. Here we show that Nhe5-deficient mice exhibit markedly enhanced learning and memory in Morris water maze, novel object recognition, and passive avoidance task. Meanwhile, the pre- and post-synaptic components, synaptophysin (Syn) and post-synaptic density 95 (PSD95) expression levels were found increased in hippocampal regions lacking of Nhe5, suggesting a possible alterations in neuronal synaptic structure and function in Nhe5(-/-) mice...
October 5, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28972541/camkii%C3%AE-suppresses-an-efferocytosis-pathway-in-macrophages-and-promotes-atherosclerotic-plaque-necrosis
#12
Amanda C Doran, Lale Ozcan, Bishuang Cai, Ze Zheng, Gabrielle Fredman, Christina C Rymond, Bernhard Dorweiler, Judith C Sluimer, Joanne Hsieh, George Kuriakose, Alan R Tall, Ira Tabas
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28972129/camkii-regulates-synaptic-nmda-receptor-activity-of-hypothalamic-presympathetic-neurons-and-sympathetic-outflow-in-hypertension
#13
De-Pei Li, Jing-Jing Zhou, Jixiang Zhang, Hui-Lin Pan
N-methyl-D-aspartate receptor (NMDAR) activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated excitatory postsynaptic currents (EPSCs) and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats...
October 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28970726/ca-2-calmodulin-dependent-protein-kinase-ii-regulates-colon-cancer-proliferation-and-migration-via-erk1-2-and-p38-pathways
#14
Wei Chen, Ping An, Xiao-Jing Quan, Jun Zhang, Zhong-Yin Zhou, Li-Ping Zou, He-Sheng Luo
AIM: To investigate the role of calmodulin-dependent protein kinase II (CaMKII) in colon cancer growth, migration and invasion. METHODS: CaMKII expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of CaMKIIin tissue samples and MMP2, MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by qRT-PCR and western blot. Cell proliferation was detected with the MTT assay...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28968141/aberrant-alterations-of-the-expressions-and-s-nitrosylation-of-calmodulin-and-the-downstream-factors-in-the-brains-of-the-rodents-during-scrapie-infection
#15
Ren-Qing Zhang, Cao Chen, Li-Jie Xiao, Jing Sun, Yue Ma, Xiao-Dong Yang, Xiao-Feng Xu, Kang Xiao, Qi Shi, Zhi-Bao Chen, Xiao-Ping Dong
The aberrant alterations of calmodulin (CaM) and its downstream substrates have been reported in some neurodegenerative diseases, but rarely described in prion disease. In this study, the potential changes of Ca(2+)/CaM and its associated agents in the brains of scrapie agent 263K-infected hamsters and the prion infected cell line SMB-S15 were evaluated by various methodologies. We found that the level of CaM in the brains of 263K-infected hamsters started to increase at early stage and maintained at high level till terminal stage...
September 3, 2017: Prion
https://www.readbyqxmd.com/read/28957669/memory-erasure-experiments-indicate-a-critical-role-of-camkii-in-memory-storage
#16
Tom Rossetti, Somdeb Banerjee, Chris Kim, Megan Leubner, Casey Lamar, Pooja Gupta, Bomsol Lee, Rachael Neve, John Lisman
The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus...
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28955223/ca-2-calmodulin-dependent-protein-kinase-ii-and-androgen-signaling-pathways-modulate-mef2-activity-in-testosterone-induced-cardiac-myocyte-hypertrophy
#17
Javier Duran, Daniel Lagos, Mario Pavez, Mayarling F Troncoso, Sebastián Ramos, Genaro Barrientos, Cristian Ibarra, Sergio Lavandero, Manuel Estrada
Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR)-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and myocyte-enhancer factor 2 (MEF2) play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX) rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28954869/the-long-3-utr-mrna-of-camkii-is-essential-for-translation-dependent-plasticity-of-spontaneous-release-in-drosophila-melanogaster
#18
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'- u n t ranslated r egion (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...
September 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28940879/phosphorylation-of-calcium-calmodulin-dependent-protein-kinase-ii-in-the-rat-dorsal-medial-prefrontal-cortex-is-associated-with-alcohol-induced-cognitive-inflexibility
#19
Luis A Natividad, Michael Q Steinman, Sarah A Laredo, Cristina Irimia, Ilham Y Polis, Robert Lintz, Matthew W Buczynski, Rémi Martin-Fardon, Marisa Roberto, Loren H Parsons
Repeated cycles of alcohol [ethanol (EtOH)] intoxication and withdrawal dysregulate excitatory glutamatergic systems in the brain and induce neuroadaptations in the medial prefrontal cortex (mPFC) that contribute to cognitive dysfunction. The mPFC is composed of subdivisions that are functionally distinct, with dorsal regions facilitating drug-cue associations and ventral regions modulating new learning in the absence of drug. A key modulator of glutamatergic activity is the holoenzyme calcium/calmodulin-dependent protein kinase II (CaMKII) that phosphorylates ionotropic glutamate receptors...
September 22, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28937250/role-of-exercise-induced-calmodulin-protein-kinase-camk-ii-activation-in-the-regulation-of-omega-6-fatty-acids-and-lipid-metabolism-genes-in-rat-skeletal-muscle
#20
J S Joseph, A O Ayeleso, E Mukwevho
Activation of calmodulin dependent protein kinase (CaMK)II by exercise is beneficial in controlling membrane lipids associated with type 2 diabetes and obesity. Regulation of lipid metabolism is crucial in the improvement of type 2 diabetes and obesity associated symptoms. The role of CaMKII in membrane associated lipid metabolism was the focus of this study. Five to six weeks old male Wistar rats were used in this study. GC×GC-TOFMS technique was used to determine the levels of polyunsaturated fatty acids (linoleic acid, arachidonic acid and 11,14-eicosadienoic acid)...
September 22, 2017: Physiological Research
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