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CaMKII 286

Ashfaq Ahmad, Tahir Ali, Hyun Young Park, Haroon Badshah, Shafiq Ur Rehman, Myeong Ok Kim
Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ1-42 mouse model of AD. Single intracerebroventricular injections of Aβ1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration...
March 5, 2016: Molecular Neurobiology
Lee Tran, N Bradley Keele
Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA...
April 15, 2016: Behavioural Brain Research
Amelia Guadalupe-Grau, Lorena Rodríguez-García, Rafael Torres-Peralta, David Morales-Álamo, Jesús Gustavo Ponce-González, Ismael Pérez-Suarez, Alfredo Santana, Jose Al Calbet
OBJECTIVES: This study was designed to investigate the association of gender, fibre type composition, and anaerobic performance with the basal skeletal muscle signalling cascades regulating muscle phenotype. DESIGN: Muscle biopsies were obtained from 25 men and 10 women all young and healthy. METHODS: Protein phosphorylation of Thr(172)AMPKα, Ser(221)ACCβ, Thr(286)CaMKII as well as total protein abundance of PGC-1α, SIRT1, and CnA were measured by Western blot and anaerobic performance by the Wingate test...
2016: European Journal of Sport Science
Xintong Lv, Feng Guo, Xiaoxue Xu, Zaixing Chen, Xuefei Sun, Dongyu Min, Yonggang Cao, Xianbao Shi, Lei Wang, Tianbao Chen, Chris Shaw, Huiling Gao, Liying Hao, Jiqun Cai
Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence‑like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+‑free solution. The expression levels of CaV1...
November 2015: Molecular Medicine Reports
Tuan A Nguyen, Pabak Sarkar, Jithesh V Veetil, Kaitlin A Davis, Henry L Puhl, Steven S Vogel
Between 8 to 14 calcium-calmodulin (Ca(2+)/CaM) dependent protein kinase-II (CaMKII) subunits form a complex that modulates synaptic activity. In living cells, the autoinhibited holoenzyme is organized as catalytic-domain pairs distributed around a central oligomerization-domain core. The functional significance of catalytic-domain pairing is not known. In a provocative model, catalytic-domain pairing was hypothesized to prevent ATP access to catalytic sites. If correct, kinase-activity would require catalytic-domain pair separation...
May 5, 2015: Biophysical Journal
Karl Peter Giese, Wajeeha Aziz, Igor Kraev, Michael G Stewart
NMDA receptor-dependent long-term potentiation (LTP) at hippocampal CA1 synapses is a well-accepted mechanism underlying long-term memory (LTM) formation. However, studies with mice that lack threonine-286 autophosphorylation of αCaMKII have shown that hippocampal LTM can be formed despite absence of NMDA receptor-dependent CA1 LTP. After multiple training trials, LTM formation in these mutants is linked to the generation of multi-innervated dendritic spines (MIS), a spine that receives typically two presynaptic inputs...
October 2015: Neurobiology of Learning and Memory
A L Frederick, H Yano, P Trifilieff, H D Vishwasrao, D Biezonski, J Mészáros, E Urizar, D R Sibley, C Kellendonk, K C Sonntag, D L Graham, R J Colbran, G D Stanwood, J A Javitch
Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C...
November 2015: Molecular Psychiatry
Y He, D Kulasiri, S Samarasinghe
A synaptic protein, Ca(2+)/Calmodulin dependent protein kinase II (CaMKII), has complex state transitions and facilitates the emergence of long term potentiation (LTP), which is highly correlated to memory formation. Two of the state transitions are critical for LTP: (1) threonine 286 autophosphorylation of CaMKII; and (2) binding to N-methyl-d-aspartate receptor (NMDAR) in the postsynaptic density (PSD) to form CaMKII-NMDAR complex. Both of these state transitions retain the activity of CaMKII when the induction signal disappears which is very important for the long-lasting characteristics of LTP...
January 21, 2015: Journal of Theoretical Biology
Xi Zhang, Quanguang Zhang, Jingyi Tu, Ying Zhu, Fang Yang, Bin Liu, Darrell Brann, Ruimin Wang
Ischemic postconditioning (Post C), which involves administration of a brief ischemia after the initial ischemic event, has been demonstrated to be strongly neuroprotective against global cerebral ischemia (GCI) and to improve cognitive outcome. To enhance understanding of the underlying mechanisms, the current study examined the role of NMDA receptors in mediating the beneficial effects of Post C (3 min ischemia) administered 2 days after GCI in adult male rats. The results revealed that Post C was strongly neuroprotective against GCI, and that this effect was blocked by administration of the NMDA receptor antagonist MK-801...
March 2015: Hippocampus
Zhaolong Liu, Gang Han, Yu Cao, Yidong Wang, Hangjun Gong
Calcium/calmodulin‑dependent protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase, involved in processes that cause tumor progression, including cell cycle regulation, apoptosis and differentiation. However, the role of CaMKII in cancer cell metastasis has not been fully elucidated. In the present study, the function of CaMKII in gastric cancer cell metastasis is reported. Firstly, it was demonstrated that the overexpression of H282R (constitutively active CaMKII) enhanced gastric cancer cell migration and invasion, and the inhibition of CaMKII activity by KN‑62 decreased gastric cancer cell metastasis...
November 2014: Molecular Medicine Reports
Liang Chen, Yanyan Miao, Lin Chen, Jing Xu, Xinxing Wang, Han Zhao, Yi Shen, Yi Hu, Yunpeng Bian, Yuanyuan Shen, Jutao Chen, Yingying Zha, Long-Ping Wen, Ming Wang
Engineered nanomaterials are known to exhibit diverse and sometimes unexpected biological effects. Fullerene nanoparticles have been reported to specifically bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca(2+) signal transduction and critical for synaptic plasticity, but the functional consequence of that modulation is unknown. Here we show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through intrahippocampal infusion and without any obvious cytotoxicity in hippocampal neuronal cells, enhance the long-term potentiation (LTP) of rats...
November 2014: Biomaterials
Steven J Coultrap, K Ulrich Bayer
Both signaling by nitric oxide (NO) and by the Ca(2+)/calmodulin (CaM)-dependent protein kinase II α isoform (CaMKIIα) are implicated in two opposing forms of synaptic plasticity underlying learning and memory, as well as in excitotoxic/ischemic neuronal cell death. For CaMKIIα, these functions specifically involve also Ca(2+)-independent autonomous activity, traditionally generated by Thr-286 autophosphorylation. Here, we demonstrate that NO-induced S-nitrosylation of CaMKIIα also directly generated autonomous activity, and that CaMKII inhibition protected from NO-induced neuronal cell death...
July 11, 2014: Journal of Biological Chemistry
Yufang Xiong, Hui Zhou, Lian Zhang
Febrile seizure (FS) remains the most common childhood neurological emergency. Although many studies have been done, controversy exists as to whether these seizures are associated with a significant risk for cognitive impairment. The aim of our study is to check whether there is a spatial learning and memory deficit in the experimental FS rats using a heated-air FS paradigm and to determine the possible molecular mechanism of cognitive impairment. On days 10 to 12 postpartum, the male rat pups were subjected to one, three, or nine episodes of brief hyperthermia-induced seizures (HS)...
April 4, 2014: Brain Research
M A Høydal, T O Stølen, A B Johnsen, M Alvez, D Catalucci, G Condorelli, L G Koch, S L Britton, G L Smith, U Wisløff
AIM: Rats selectively bred for inborn low capacity of running (LCR) display a series of poor health indices, whereas rats selected for high capacity of running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca(2+) leak that trigger arrhythmia. METHODS: We used rats selected for HCR (N = 10) or LCR (N = 10) to determine the effect of inborn aerobic capacity on Ca(2+) leak and susceptibility of ventricular arrhythmia...
April 2014: Acta Physiologica
Xin-Tai Wang, Xia Lian, Ying-Ming Xu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Intrathecal application of α2 noradrenergic receptor agonists effectively alleviates the pathological pain induced by peripheral tissue injury. However, the spinal antinociceptive mechanisms of α2 noradrenergic receptors remain to be characterized. The present study performed immunohistochemistry and western blot to elucidate the signaling pathway initiated by α2 noradrenergic receptors in spinal dorsal horn of mice, and identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an important target for noradrenergic suppression of inflammatory pain...
February 5, 2014: European Journal of Pharmacology
B Banerjee, B K Medda, S Pochiraju, P Kannampalli, I M Lang, J N Sengupta, R Shaker
BACKGROUND: We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices...
December 2013: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Yanwei Xing, Yonghong Gao, Jianxin Chen, Haiyan Zhu, Aiming Wu, Qing Yang, Fei Teng, Dong-Mei Zhang, Yanhui Xing, Kuo Gao, Qingyong He, Zhenpeng Zhang, Jie Wang, Hongcai Shang
Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of the α - and β -adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction...
2013: Evidence-based Complementary and Alternative Medicine: ECAM
Yong-Hoon Kim, Jung Hwan Hwang, Kyung-Shim Kim, Jung-Ran Noh, Gil-Tae Gang, Sang-Woo Kim, Seung Pil Jang, Sang-Ju Lee, Sung-Ho Her, Kyeong-Hoon Jeong, Tae Hwan Kwak, Woo Jin Park, Irina V Balyasnikova, Minho Shong, Chul-Ho Lee
AIMS: Angiotensin-converting enzyme (ACE) plays a key role in blood pressure (BP) homeostasis via regulation of angiotensin II. Active ACE ectodomain is enzymatically cleaved and released into body fluids, including plasma, and elevated plasma ACE levels are associated with increased BP. β-lapachone (βL) has been shown to increase cellular NAD(+)/NADH ratio via activation of NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, we evaluated whether NQO1 activation by βL modulates BP through regulation of ACE shedding in an animal model of hypertension...
September 1, 2013: Cardiovascular Research
Heidi Kaastrup Müller, Gregers Wegener, Nico Liebenberg, Carlos A Zarate, Maurizio Popoli, Betina Elfving
In the search for new drug targets, that may help point the way to develop fast-acting treatments for mood disorders, we have explored molecular pathways regulated by ketamine, an NMDA receptor antagonist, which has consistently shown antidepressant response within a few hours of administration. Using Sprague-Dawley rats we investigated the effects of ketamine on the presynaptic release machinery responsible for neurotransmitter release at 1, 2 and 4 h as well as 7 days after administration of a single subanesthetic dose of ketamine (15 mg/kg)...
July 2013: Journal of Psychiatric Research
Shigeki Moriguchi, Tomoya Tanaka, Hideaki Tagashira, Toshio Narahashi, Kohji Fukunaga
Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice...
April 1, 2013: Behavioural Brain Research
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