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"camkii" OR "calcium/calmodulin dependent kinase type II"

S Moriguchi, T Ishizuka, Y Yabuki, N Shioda, Y Sasaki, H Tagashira, H Yawo, J Z Yeh, H Sakagami, T Narahashi, K Fukunaga
Here, we report a novel target of the drug memantine, ATP-sensitive K(+) (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer's model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhancement of hippocampal long-term potentiation (LTP) and CaMKII activity was totally abolished by treatment with pinacidil, a specific opener of KATP channels. Memantine also inhibited Kir6.1 and Kir6...
October 25, 2016: Molecular Psychiatry
Manel Ben Aissa, Sue H Lee, Brian M Bennett, Gregory R J Thatcher
cAMP-response element-binding protein (CREB) plays a central role in various aspects of central nervous system (CNS) function, ranging from the developmental stages to neuronal plasticity and survival in adult brain. Activation of CREB plays a crucial role in learning and memory and is at the convergence of multiple intracellular signaling cascades including CAMKII and MAPK. This review focuses on the important functions of nitric oxide (NO) in activating CREB via the NO receptor, soluble guanylyl cyclase (sGC), and production of the second messenger, cGMP...
2016: Current Medicinal Chemistry
Hao Huang, Linfu Li, Weimei Shi, Hai Liu, Jianqiong Yang, Xiaoliang Yuan, Longhuo Wu
Nobiletin (NOB) chemically known as 5,6,7,8,3',4'-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca(2+)/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Xiao-Juan Wang, Yin-Ping Gao, Nan-Nan Lu, Wei-Shuo Li, Ji-Fang Xu, Xiao-Ying Ying, Gang Wu, Mei-Hua Liao, Chao Tan, Ling-Xiao Shao, Ying-Mei Lu, Chen Zhang, Kohji Fukunaga, Feng Han, Yong-Zhong Du
Clinical treatment for vascular dementia still remains a challenge mainly due to Blood-Brain Barrier (BBB). Here, a micelle based on polysialic acid (PSA) which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was firstly chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behaviour over a period of 72 h with 3...
October 17, 2016: ACS Applied Materials & Interfaces
Przemysław B Radwański, Hsiang-Ting Ho, Rengasayee Veeraraghavan, Lucia Brunello, Bin Liu, Andriy E Belevych, Sathya D Unudurthi, Michael A Makara, Silvia G Priori, Pompeo Volpe, Antonis A Armoundas, Wolfgang H Dillmann, Bjorn C Knollmann, Peter J Mohler, Thomas J Hund, Sándor Györke
BACKGROUND: Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca(2+) and Na(+) handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive. METHODS AND RESULTS: We performed functional and structural studies to assess Ca(2+) and Na(+) signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT...
June 2016: JACC. Basic to Translational Science
Yong Xie, Zhen-Jie Gu, Mao-Xiong Wu, Tu-Cheng Huang, Jing-Song Ou, Huiping-Son Ni, Mao-Huan Lin, Wo-Liang Yuan, Jing-Feng Wang, Yang-Xin Chen
AIMS: Adverse cardiovascular effects induced by peroxisome proliferator activator receptor-γ (PPAR-γ) activation were observed in clinical setting. But the underlying mechanism is unclear. Now, transgenic mice with cardiac specific peroxisome proliferator activator receptor-γ overexpression (TG-PPAR-γ) were used to explore the possible mechanisms. MATERIALS AND METHODS: Cardiac tissues from TG-PPAR-γ mice, a PPAR-γ over-expressing human cardiomyocyte line AC16 cell, and PPAR-γ agonist-treated primary cardiomyocytes were used to evaluate the expression of cardiac calcium regulatory proteins as sarcoplasmic reticulum Ca(2+) ATPase, Na(+)/Ca(2+)exchanger 1, ryanodine receptor 2 and phospholamban...
October 13, 2016: Life Sciences
Santhanalakshmi Sundaramurthy, Balasubramaniam Annamalai, Devadoss J Samuvel, Toni S Shippenberg, Lankupalle D Jayanthi, Sammanda Ramamoorthy
Kappa opioid receptor (KOR) agonists produce dysphoria and psychotomimesis. While KOR agonists produce pro-depressant-like effects, KOR antagonists produce anti-depressant-like effects in rodent models. The cellular mechanisms and downstream effector(s) by which KOR ligands produce these effects are not clear. KOR agonists modulate serotonin (5-HT) transmission in the brain regions implicated in mood and motivation regulation. Presynaptic serotonin transporter (SERT) activity is critical in the modulation of synaptic 5-HT and, subsequently, in mood disorders...
October 12, 2016: Neuropharmacology
Amy E Mendham, Rob Duffield, Aaron J Coutts, Frank E Marino, Andriy Boyko, Andrew J McAinch, David John Bishop
PURPOSE: This study assessed the mitochondrial related signaling responses to a single bout of non-contact, modified football (touch rugby), played as small-sided games (SSG), or cycling (CYC) exercise in sedentary, obese, middle-aged men. METHOD: In a randomized, cross-over design, nine middle-aged, sedentary, obese men completed two, 40-min exercise conditions (CYC and SSG) separated by a 21-d recovery period. Heart rate (HR) and Ratings of Perceived Exertion were collected during each bout...
October 14, 2016: Journal of Applied Physiology
Julian Mustroph, Stefan Neef, Lars S Maier
Calcium/calmodulin-dependent protein kinase II (CaMKII) has emerged as key enzyme in many cardiac pathologies, especially heart failure (HF), myocardial infarction and cardiomyopathies, thus leading to contractile dysfunction and malignant arrhythmias. While many pathways leading to CaMKII activation have been elucidated in recent years, hardly any clinically viable compounds affecting CaMKII activity have progressed from basic in vitro science to in vivo studies. This review focuses on recent advances in anti-arrhythmic strategies involving CaMKII...
October 11, 2016: Pharmacology & Therapeutics
W Ma, B St-Jacques, U Rudakou, Y N Kim
BACKGROUND: Persistent peripheral sensitization contributes to chronic pain. Plasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to sensitization. Prostaglandin E2 (PGE2) enriched in injured tissues is known not only directly to sensitize DRG neurons, but also to potentiate sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It remains unknown whether PGE2 potentiates TRPV1 activity by stimulating its synthesis, cell surface and axonal trafficking in DRG neurons...
October 14, 2016: European Journal of Pain: EJP
Pengwei Zhuang, Yingying Huang, Zhiqiang Lu, Zhen Yang, Liman Xu, Fengjiao Sun, Yanjun Zhang, Jinao Duan
Aconiti Lateralis Radix Praeparata (Fuzi) and Fritillariae Thunbergii bulbus (Beimu) have been widely used clinically to treat cardiopulmonary related diseases in China. However, according to the classic rules of traditional Chinese medicine, Fuzi and Beimu should be prohibited to use as a combination for their incompatibility. Therefore, it is critical to elucidate the paradox on the use of Fuzi and Beimu combination therapy. Monocrotaline-induced pulmonary hypertension rats were treated with either Fuzi, Beimu, or their combination at different stages of PH...
October 14, 2016: Scientific Reports
Shangcheng Xu, Pei Wang, Huiliang Zhang, Guohua Gong, Nicolas Gutierrez Cortes, Weizhong Zhu, Yisang Yoon, Rong Tian, Wang Wang
Mitochondrial permeability transition pore (mPTP) is involved in cardiac dysfunction during chronic β-adrenergic receptor (β-AR) stimulation. The mechanism by which chronic β-AR stimulation leads to mPTP openings is elusive. Here, we show that chronic administration of isoproterenol (ISO) persistently increases the frequency of mPTP openings followed by mitochondrial damage and cardiac dysfunction. Mechanistically, this effect is mediated by phosphorylation of mitochondrial fission protein, dynamin-related protein 1 (Drp1), by Ca(2+)/calmodulin-dependent kinase II (CaMKII) at a serine 616 (S616) site...
October 14, 2016: Nature Communications
Ji Hye Park, Sung Hyun Choi, Hyungtae Kim, Seung Taek Ji, Woong Bi Jang, Jae Ho Kim, Sang Hong Baek, Sang Mo Kwon
Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs...
October 9, 2016: International Journal of Molecular Sciences
Jisung Kim, Siyoung Lee, Bo-Ryoung Choi, Hee Yang, Youjin Hwang, Jung Han Yoon Park, Frank M LaFerla, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane...
October 13, 2016: Molecular Nutrition & Food Research
Richard Cv Tyser, Antonio Ma Miranda, Chiann-Mun Chen, Sean M Davidson, Shankar Srinivas, Paul R Riley
The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca(2+)-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8...
October 11, 2016: ELife
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Cheng-Chih Chung, Ting-I Lee, Wen-Chin Tsai, Shih-Ann Chen, Yi-Jen Chen
Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0...
October 4, 2016: Oncotarget
Yan Wu, Meng-Yu He, Jian-Kui Ye, Shu-Ying Ma, Wen Huang, Yong-Yue Wei, Hui Kong, Hong Wang, Xiao-Ning Zeng, Wei-Ping Xie
Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation...
October 6, 2016: Journal of Cellular and Molecular Medicine
Ila Pant, S Girish Rao, Paturu Kondaiah
Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-β driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-β activation and its effects contributing to OSF. However, the mechanism for activation of TGF-β signaling in OSF is still unknown. In this study we demonstrate activation of TGF-β signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process...
October 6, 2016: Scientific Reports
Akiya Watakabe, Osamu Sadakane, Katsusuke Hata, Masanari Ohtsuka, Masafumi Takaji, Tetsuo Yamamori
It is important to study the neural connectivities and functions in primates. For this purpose, it is critical to be able to transfer genes to certain neurons in the primate brain so that we can image the neuronal signals and analyze the function of the transferred gene. Toward this end, our team has been developing gene transfer systems using viral vectors. In this review, we summarize our current achievements as follows. 1) We compared the features of gene transfer using five different AAV serotypes in combination with three different promoters, namely, CMV, mouse CaMKII (CaMKII), and human synapsin 1 (hSyn1), in the marmoset cortex with those in the mouse and macaque cortices...
October 5, 2016: Developmental Neurobiology
Tianzhi Huang, Angel A Alvarez, Rajendra P Pangeni, Craig M Horbinski, Songjian Lu, Sung-Hak Kim, C David James, Jeffery J Raizer, John A Kessler, Cameron W Brenann, Erik P Sulman, Gaetano Finocchiaro, Ming Tan, Ryo Nishikawa, Xinghua Lu, Ichiro Nakano, Bo Hu, Shi-Yuan Cheng
Molecularly defined subclassification is associated with phenotypic malignancy of glioblastoma (GBM). However, current understanding of the molecular basis of subclass conversion that is often involved in GBM recurrence remain rudimentary at best. Here we report that canonical Wnt signalling that is active in proneural (PN) but inactive in mesenchymal (MES) GBM, along with miR-125b and miR-20b that are expressed at high levels in PN compared with MES GBM, comprise a regulatory circuit involving TCF4-miR-125b/miR-20b-FZD6...
October 4, 2016: Nature Communications
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