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

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https://www.readbyqxmd.com/read/28437279/npy-impairs-cell-viability-and-mitochondrial-membrane-potential-through-ca2-and-p38-signaling-pathways-in-neonatal-rat-cardiomyocytes
#1
Jun Hu, Xuehua Xu, Yuanyi Zuo, Xiangting Gao, Yun Wang, Cunquan Xiong, Hongcheng Zhou, Shaohua Zhu
NPY is involved in stress cardiomyopathy (SCM). However, the associated mechanism for NPY-induced SCM remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, the expression of CaN and p-CAMKII was increased significantly, and the phosphorylation of p38 but not ERK and JNK was detected...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28436159/the-mechanism-research-of-hypoxia-induced-increased-late-sodium-current-resulting-in-intracellular-ca-2-overload-in-ventricular-myocytes
#2
Chen Fu, Jie Hao, Mengliu Zeng, Yejia Song, Wanzhen Jiang, Peihua Zhang, Antao Luo, Zhenzhen Cao, Luiz Belardinelli, Jihua Ma
Hypoxia leads to augmentation of late sodium current (INa.L ) and cellular Na(+) loading, increased reverse Na(+) -Ca(2+) exchange current (reverse INCX ) and intracellular Ca(2+) loading in rabbit ventricular myocytes. The purpose of this study was to determine the intracellular signal transduction pathways involved in the modulation of INa.L during hypoxia in ventricular myocytes. Whole-cell and cell-attached patch clamp techniques were used to record INa.L , and the whole-cell mode was also used to record reverse INCX and to study intercellular signal transduction mechanisms that mediate the increased INa...
April 24, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#3
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
https://www.readbyqxmd.com/read/28430606/ketamine-administered-pregnant-rats-impair-learning-and-memory-in-offspring-via-the-creb-pathway
#4
Xinran Li, Cen Guo, Yanan Li, Lina Li, Yuxin Wang, Yiming Zhang, Yue Li, Yu Chen, Wenhan Liu, Li Gao
Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428622/inhibition-of-late-sodium-current-suppresses-calcium-related-ventricular-arrhythmias-by-reducing-the-phosphorylation-of-camk-ii-and-sodium-channel-expressions
#5
Xiao-Hong Wei, Shan-Dong Yu, Lu Ren, Si-Hui Huang, Qiao-Mei Yang, Ping Wang, Yan-Peng Chu, Wei Yang, Yan-Sheng Ding, Yong Huo, Lin Wu
Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration ([Ca(2+)]i) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423675/mir-219-5p-targets-camkii%C3%AE-to-attenuate-morphine-tolerance-in-rats
#6
Jian Wang, Wei Xu, Jiali Shao, Zhenghua He, Zhuofeng Ding, Jiangju Huang, Qulian Guo, Wangyuan Zou
Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421673/endothelial-erbb4-deficit-induces-alterations-in-exploratory-behavior-and-brain-energy-metabolism-in-mice
#7
Gang Wu, Xiu-Xiu Liu, Nan-Nan Lu, Qi-Bing Liu, Yun Tian, Wei-Feng Ye, Guo-Jun Jiang, Rong-Rong Tao, Feng Han, Ying-Mei Lu
AIMS: The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. RESULTS: Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in CaMKII phosphorylation in Cdh5Cre;ErbB4(f/f) mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits...
April 18, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28404629/braf-signaling-principles-unveiled-by-large-scale-human-mutation-analysis-with-a-rapid-lentivirus-based-gene-replacement-method
#8
Chae-Seok Lim, Xi Kang, Vincent Mirabella, Huaye Zhang, Qian Bu, Yoichi Araki, Elizabeth T Hoang, Shiqiang Wang, Ying Shen, Sukwoo Choi, Bong-Kiun Kaang, Qiang Chang, Zhiping P Pang, Richard L Huganir, J Julius Zhu
Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene mutation-cell behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28400318/hemopexin-counteracts-systolic-dysfunction-induced-by-heme-driven-oxidative-stress
#9
Giada Ingoglia, Can Martin Sag, Nikolai Rex, Lucia De Franceschi, Francesca Vinchi, James Cimino, Sara Petrillo, Stefan Wagner, Klaus Kreitmeier, Lorenzo Silengo, Fiorella Altruda, Lars S Maier, Emilio Hirsch, Alessandra Ghigo, Emanuela Tolosano
Heart failure is a leading cause of morbidity and mortality in patients affected by different disorders associated to intravascular hemolysis. The leading factor is the presence of pathologic amount of pro-oxidant free heme in the bloodstream, due to the exhaustion of the natural heme scavenger Hemopexin (Hx). Here, we evaluated whether free heme directly affects cardiac function, and tested the therapeutic potential of replenishing serum Hx for increasing serum heme buffering capacity. The effect of heme on cardiac function was assessed in vitro, on primary cardiomyocytes and H9c2 myoblast cell line, and in vivo, in Hx(-/-) mice and in genetic and acquired mouse models of intravascular hemolysis...
April 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28392472/nf-l-in-cerebrospinal-fluid-and-serum-is-a-biomarker-of-neuronal-damage-in-an-inducible-mouse-model-of-neurodegeneration
#10
Anthony Brureau, Véronique Blanchard-Bregeon, Catherine Pech, Stéphanie Hamon, Pascal Chaillou, Jean-Claude Guillemot, Pascal Barneoud, Philippe Bertrand, Laurent Pradier, Thomas Rooney, Nathalie Schussler
Accumulation of neurofilaments (NFs), the major constituents of the neuronal cytoskeleton, is a distinctive feature of neurological diseases and several studies have shown that soluble NFs can be detected in the cerebrospinal fluid (CSF) of patients with neurological diseases, such as multiple sclerosis and frontotemporal dementia. Here we have used an inducible transgenic mouse model of neurodegeneration, CamKII-TetOp25 mice, to evaluate whether NF-L levels in CSF or blood can be used as a biochemical biomarker of neurodegeneration...
April 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28387756/pore-forming-toxin-mediated-ion-dysregulation-leads-to-death-receptor-independent-necroptosis-of-lung-epithelial-cells-during-bacterial-pneumonia
#11
Norberto González-Juarbe, Kelley Margaret Bradley, Anukul Taranath Shenoy, Ryan Paul Gilley, Luis Felipe Reyes, Cecilia Anahí Hinojosa, Marcos Ignacio Restrepo, Peter Herman Dube, Molly Ann Bergman, Carlos Javier Orihuela
We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively...
April 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28382978/long-term-treatment-with-intranasal-insulin-ameliorates-cognitive-impairment-tau-hyperphosphorylation-and-microglial-activation-in-a-streptozotocin-induced-alzheimer-s-rat-model
#12
Zhangyu Guo, Yanxing Chen, Yan-Fang Mao, Tingting Zheng, Yasi Jiang, Yaping Yan, Xinzhen Yin, Baorong Zhang
Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer's disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379303/restoring-neuronal-progranulin-reverses-deficits-in-a-mouse-model-of-frontotemporal-dementia
#13
Andrew E Arrant, Anthony J Filiano, Daniel E Unger, Allen H Young, Erik D Roberson
Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotional behaviour. GRN mutations are thought to cause frontotemporal dementia through progranulin haploinsufficiency, therefore, boosting progranulin expression from the intact allele is a rational treatment strategy. However, this approach has not been tested in an animal model of frontotemporal dementia and it is unclear if boosting progranulin could correct pre-existing deficits...
March 29, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28376888/daily-administration-of-yokukansan-and-keishito-prevents-social-isolation-induced-behavioral-abnormalities-and-down-regulation-of-phosphorylation-of-neuroplasticity-related-signaling-molecules-in-mice
#14
COMPARATIVE STUDY
Hironori Fujiwara, Yaoyu Han, Ken Ebihara, Suresh Awale, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto
BACKGROUND: Our previous studies demonstrated that post-weaning social isolation (ISO) in mice induces behavior abnormalities such as deficits of sociability- and attention-like behaviors. These deficits can be attenuated by methylphenidate (MPH), a drug used for attention deficit hyperactivity disorder (ADHD), suggesting that ISO mice offer a potential animal model of comorbid developmental disorder with ADHD and autism spectrum disorder symptoms. This study investigated the effects of Kampo formulae, yokukansan (YKS) and keishito (KST), on the neuropsychiatric symptoms of ISO mice to clarify the therapeutic or preventive/delaying potential of these formulae for the treatment of neurodevelopmental disorders...
April 4, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28376667/environmental-enrichment-mitigates-deficits-after-repetitive-mild-tbi
#15
Xiaxia Liu, Jianhua Qiu, Sasha Alcon, Jumana Hashim, William Meehan, Rebekah Mannix
While environmental enrichment has been shown to improve functional and histologic outcomes in preclinical moderate-severe traumatic brain injury (TBI), there is a paucity of preclinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance...
April 4, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28374413/beneficial-effects-of-leptin-treatment-in-a-setting-of-cardiac-dysfunction-induced-by-transverse-aortic-constriction-in-mouse
#16
Nieves Gómez-Hurtado, Alejandro Domínguez-Rodríguez, Philippe Mateo, Maria Fernandez-Velasco, Almudena Val-Blasco, Rafael Aizpún, Jessica Sabourin, Ana Maria Gómez, Jean-Pierre Benitah, Carmen Delgado
KEY POINTS: Leptin, is a 16 kDa pleiotropic peptide, primary secreted by adipocytes, but also produced by other tissues including the heart. Controversy exists regarding the adverse and beneficial effects of Leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca(2+) ]i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction We find that Leptin activates mechanisms that contribute to cardiac dysfunction in physiological conditions...
April 4, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28371191/structure-based-target-specific-screening-leads-to-small-molecule-camkii-inhibitors
#17
David Xu, Liwei Li, Donghui Zhou, Degang Liu, Andy Hudmon, Samy O Meroueh
Target-specific scoring methods are more commonly used to identify small-molecule inhibitors among compounds docked to a target of interest. Top candidates that emerge from these methods have rarely been tested for activity and specificity across a family of proteins. In this study we docked a chemical library into CaMKIIδ, a member of the Ca(2+) /calmodulin (CaM)-dependent protein kinase (CaMK) family, and re-scored the resulting protein-compound structures using Support Vector Machine SPecific (SVMSP), a target-specific method that we developed previously...
March 29, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28363984/blood-pressure-regulation-by-the-rostral-ventrolateral-medulla-in-conscious-rats-effects-of-hypoxia-hypercapnia-baroreceptor-denervation-and-anesthesia
#18
Ian C Wenker, Chikara Abe, Kenneth E Viar, Daniel S Stornetta, Ruth L Stornetta, Patrice G Guyenet
Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments carried out in anesthetized animals or reduced ex vivo preparations. Here we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact unanesthetized rats. Using a lentivirus that expresses ArchT under the Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ∼65% of transduced neurons were C1 (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28361052/camkii-signaling-stimulates-mef2c-activity-in-vitro-but-only-minimally-affects-murine-long-bone-development-in-vivo
#19
Chandra S Amara, Christine Fabritius, Astrid Houben, Lena I Wolff, Christine Hartmann
The long bones of vertebrate limbs form by endochondral ossification, whereby mesenchymal cells differentiate into chondrogenic progenitors, which then differentiate into chondrocytes. Chondrocytes undergo further differentiation from proliferating to prehypertrophic, and finally to hypertrophic chondrocytes. Several signaling pathways and transcription factors regulate this process. Previously, we and others have shown in chicken that overexpression of an activated form of Calcium/calmodulin-dependent kinase II (CaMKII) results in ectopic chondrocyte maturation...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28360100/trans-fatty-acids-promote-proinflammatory-signaling-and-cell-death-by-stimulating-the-apoptosis-signal-regulating-kinase-1-ask1-p38-pathway
#20
Yusuke Hirata, Miki Takahashi, Yuki Kudoh, Kuniyuki Kano, Hiroki Kawana, Kumiko Makide, Yasuharu Shinoda, Yasushi Yabuki, Kohji Fukunaga, Junken Aoki, Takuya Noguchi, Atsushi Matsuzawa
Food-borne trans-fatty acids (TFAs) are mainly produced as byproducts during food manufacture. Recent epidemiological studies have revealed that TFA consumption is a major risk factor for various disorders, including atherosclerosis. However, the underlying mechanisms in this disease etiology are largely unknown. Here, we have shown that TFAs potentiate activation of apoptosis signal-regulating kinase 1 (ASK1) induced by extracellular ATP, a damage-associated molecular pattern (DAMP) leaked from injured cells...
March 29, 2017: Journal of Biological Chemistry
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