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https://www.readbyqxmd.com/read/28102477/potential-new-mechanisms-of-pro-arrhythmia-in-arrhythmogenic-cardiomyopathy-focus-on-calcium-sensitive-pathways
#1
REVIEW
C J M van Opbergen, M Delmar, T A B van Veen
Arrhythmogenic cardiomyopathy, or its most well-known subform arrhythmogenic right ventricular cardiomyopathy (ARVC), is a cardiac disease mainly characterised by a gradual replacement of the myocardial mass by fibrous and fatty tissue, leading to dilatation of the ventricular wall, arrhythmias and progression towards heart failure. ARVC is commonly regarded as a disease of the intercalated disk in which mutations in desmosomal proteins are an important causative factor. Interestingly, the Dutch founder mutation PLN R14Del has been identified to play an additional, and major, role in ARVC patients within the Netherlands...
January 19, 2017: Netherlands Heart Journal
https://www.readbyqxmd.com/read/28101169/role-of-wnt-%C3%AE-catenin-wnt-c-jun-n-terminal-kinase-and-wnt-ca-2-pathways-in-cisplatin-induced-chemoresistance-in-ovarian-cancer
#2
Lu Huang, Ye Jin, Shujun Feng, Yuqing Zou, Sainan Xu, Shuang Qiu, Ling Li, Jianhua Zheng
The aim of the present study was to explore the expression of Wnt signaling proteins β-catenin, c-Jun N-terminal kinase (JNK) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin-induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR-99021, glycogen synthase kinase 3β inhibitor) or inhibitor (XAV-939, tankyrase inhibitor)...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28097237/oxidized-camkii-promotes-asthma-through-the-activation-of-mast-cells
#3
Jingjing Qu, Danh C Do, Yufeng Zhou, Elizabeth Luczak, Wayne Mitzner, Mark E Anderson, Peisong Gao
Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096498/differential-changes-in-hippocampal-camkii-and-glua1-activity-after-memory-training-involving-different-levels-of-adaptive-forgetting
#4
Nicolas Fraize, Al Mahdy Hamieh, Mickaël Antoine Joseph, Monique Touret, Régis Parmentier, Paul Antoine Salin, Gaël Malleret
Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference...
February 2017: Learning & Memory
https://www.readbyqxmd.com/read/28096195/the-multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#5
Loubina Fazal, Marion Laudette, Sílvia Paula-Gomes, Sandrine Pons, Caroline Conte, Florence Tortosa, Pierre Sicard, Yannis Sainte-Marie, Malik Bisserier, Olivier Lairez, Alexandre Lucas, Jérôme Roy, Bijan Ghaleh, Jeremy Fauconnier, Jeanne Mialet-Perez, Frank Lezoualc'h
RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of mitochondrial exchange protein directly activated by cAMP 1 (MitEpac1) in ischemia/reperfusion (I/R) injury...
January 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28094445/presynaptic-inhibition-of-transient-receptor-potential-vanilloid-type-1-trpv1-receptors-by-norepinephrine-in-nociceptive-neurons
#6
Saikat Chakraborty, Vincent Elvezio, Martin Kaczocha, Mario Rebecchi, Michelino Puopolo
The transient receptor potential vanilloid type 1 (TRPV1) receptor is a well-known contributor to nociceptor excitability. To address whether norepinephrine can down-regulate TRPV1 channel activity in nociceptors and reduce their synaptic transmission, the effects of norepinephrine and clonidine were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons and on miniature excitatory postsynaptic currents (mEPSCs) recorded from large lamina I neurons in horizontal spinal cord slices...
January 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28069946/wnt5a-is-essential-for-hippocampal-dendritic-maintenance-and-spatial-learning-and-memory-in-adult-mice
#7
Chih-Ming Chen, Lauren L Orefice, Shu-Ling Chiu, Tara A LeGates, Samer Hattar, Richard L Huganir, Haiqing Zhao, Baoji Xu, Rejji Kuruvilla
Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065796/ischaemia-and-excitotoxicity-induced-camkii-mediated-neuronal-cell-death-the-relative-roles-of-camkii-autophosphorylation-at-t286-and-t253
#8
John A P Rostas, Alexander Hoffman, Lucy A Murtha, Debbie Pepperall, Damian D McLeod, Phillip W Dickson, Neil J Spratt, Kathryn A Skelding
Ischaemia/excitotoxicity produces persistent activation of CaMKII (Ca(2+)-calmodulin stimulated protein kinase II) that initiates cell death. This study investigated the involvement of CaMKII phosphorylation at T286 and T253 in producing this persistent activation. In T286A-αCaMKII transgenic mice that lack the ability to phosphorylate αCaMKII at T286, transient occlusion of the middle cerebral artery for 90 min resulted in no significant difference in infarct size compared to normal littermate controls...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28065733/amelioration-of-apelin-13-in-chronic-normobaric-hypoxia-induced-anxiety-like-behavior-is-associated-with-an-inhibition-of-nf-%C3%AE%C2%BAb-in-the-hippocampus
#9
Junming Fan, Lu Ding, Dongmei Xia, Danyang Chen, Pu Jiang, Wenhua Ge, Ru Zhao, Jinbin Guo, Xiaofang Fan, Feng Xue, Yongyu Wang, Sunzhong Mao, Lianggang Hu, Yongsheng Gong
Apelin, a small bioactive peptide, plays an important role in the pathogenesis of mood disorders through the endogenous ligand APJ. Although the anxiolytic effect of apelin is well established, the mechanisms are poorly understood. In this study, we hypothesized that apelin played an anxiolytic role in chronic normobaric hypoxia (CNH)-induced anxiety like behavior in mice, which might be associated with an inhibition of nuclear factor-κB (NF-κB) activation in the hippocampus. To this end, mice were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2, ∼10%, 23h/d) with or without apelin-13 application (20 nmol...
January 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28059801/repeated-anodal-transcranial-direct-current-stimulation-induces-neural-plasticity-associated-gene-expression-in-the-rat-cortex-and-hippocampus
#10
Min Sun Kim, Ho Koo, Sang Who Han, Walter Paulus, Michael A Nitsche, Yun-Hee Kim, Jin A Yoon, Yong-Il Shin
BACKGROUND: Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. OBJECTIVE: The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. METHODS: We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days...
January 4, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28051144/deep-transcriptomic-profiling-of-m1-macrophages-lacking-trpc3
#11
Sivarajan Kumarasamy, Sumeet Solanki, Oluwatomisin T Atolagbe, Bina Joe, Lutz Birnbaumer, Guillermo Vazquez
In previous studies using mice with macrophage-specific loss of TRPC3 we found a significant, selective effect of TRPC3 on the biology of M1, or inflammatory macrophages. Whereas activation of some components of the unfolded protein response and the pro-apoptotic mediators CamkII and Stat1 was impaired in Trpc3-deficient M1 cells, gathering insight about other molecular signatures within macrophages that might be affected by Trpc3 expression requires an alternative approach. In the present study we conducted RNA-seq analysis to interrogate the transcriptome of M1 macrophages derived from mice with macrophage-specific loss of TRPC3 and their littermate controls...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28051103/maladaptive-sex-behavior-following-concurrent-methamphetamine-and-sexual-experience-in-male-rats-is-associated-with-altered-neural-activity-in-frontal-cortex
#12
Lindsey B Kuiper, Karla S Frohmader, Lique M Coolen
The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated that methamphetamine (Meth), when administered concurrently with sexual behavior show impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior and the effects of concurrent Meth and sexual behavior on neural activity in these pathways, using ERK phosphorylation (pERK) as neural activity marker...
January 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28049192/combined-memantine-and-donepezil-treatment-improves-behavioral-and-psychological-symptoms-of-dementia-like-behaviors-in-olfactory-bulbectomized-mice
#13
Yasushi Yabuki, Kazuya Matsuo, Koga Hirano, Yasuharu Shinoda, Shigeki Moriguchi, Kohji Fukunaga
Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed...
January 4, 2017: Pharmacology
https://www.readbyqxmd.com/read/28049027/an-integrated-shotgun-proteomics-and-bioinformatics-approach-for-analysis-of-brain-proteins-from-mcao-model-using-serial-affinity-chromatograph-with-four-active-ingredients-from-shengmai-preparations-as-ligands
#14
Xiao-Xue Fan, Fang Li, Yan-Ni Lv, Yu Zhang, Jun-Ping Kou, Bo-Yang Yu
Identification and validation of disease-relevant target proteins for natural products is an essential component of modern pharmaceutical research. In the present study, an integrated shotgun proteomics and bioinformatics approach was established to profile the interaction of active small molecules derived from ShengMai preparations (SMXZF) with hundreds of endogenously expressed proteins from middle cerebral artery occlusion (MCAO) model. Affinity-based proteomic strategies for isolation and identification of targets for the bioactive components is a classic, but still powerful approach...
January 1, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28039202/caveolae-specific-activation-loop-between-camkii-and-l-type-ca2-channel-aggravates-cardiac-hypertrophy-in-%C3%AE-1-adrenergic-stimulation
#15
Kota Tonegawa, Wataru Otsuka, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu, Shota Tanaka, Kazumasa Moriwaki, Masanori Obana, Makiko Maeda, Michio Asahi, Hiroshi Kiyonari, Yasushi Fujio, Hiroyuki Nakayama
AIMS: Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many CaMKII targets, including L-type Ca2+ channel (LTCC) complex, and serves as a signalling platform. The location of CaMKII activation is thought to be critical, however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae, and to determine the functional role of caveolar CaMKII in cardiac hypertrophy...
December 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28039086/camkii-requirement-for-the-persistence-of-in-vivo-hippocampal-mossy-fiber-synaptic-plasticity-and-structural-reorganization
#16
Yectivani Juárez-Muñoz, Alejandro Rivera-Olvera, Laura E Ramos-Languren, Martha L Escobar
CaMKII has been proposed as a molecular substrate for long-term memory storage due to its capacity to maintain an active autophosporylated state even after the decay of the external stimuli. The hippocampal mossy fiber-CA3 pathway (MF-CA3) is considered as a relevant area for acquisition and storage of different learning tasks. MF-CA3 pathway exhibits a form of LTP characterized by a slow initial increase in the EPSP slope that is independent of NMDA receptors activation. Our previous studies show that application of high frequency stimulation sufficient to elicit MF-CA3 LTP produces structural reorganization, in a manner independent of LTP induction, at the stratum oriens of hippocampal CA3 area 7days after stimulation...
December 27, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28035181/functional-connectivity-of-basolateral-amygdala-neurons-carrying-orexin-receptors-and-melanin-concentrating-hormone-receptors-in-regulating-sociability-and-mood-related-behaviors
#17
Tae-Kyung Kim, Pyung-Lim Han
Chronic stress induces changes in neuronal functions in specific brain regions regulating sociability and mood-related behaviors. Recently we reported that stress-induced persistent upregulation of the neuropeptides orexin and melanin-concentrating hormone (MCH) in the basolateral amygdala (BLA) and the resulting activation of orexin receptors or MCH receptors within the BLA produced deficits in sociability and mood-related behaviors. In the present study, we investigated the neural targets that were innervated by BLA neurons containing orexin receptors or MCH receptors...
December 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/28033307/effect-of-sodium-valproate-on-cognitive-function-and-hippocampus-of-rats-after-convulsive-status-epilepticus
#18
Peng Wu, Siqi Hong, Min Zhong, Yi Guo, Hengsheng Chen, Li Jiang
BACKGROUND The aim of this study was to explore the effect and possible mechanism of sodium valproate (VPA) on the cognitive function and the hippocampus of rats after convulsive status epilepticus (CES). MATERIAL AND METHODS A rat model of CES was established and the Morris water maze was used to observe changes in the cognitive function of the rats after the administration of VPA. Acute hippocampal slices were made to detect field excitatory postsynaptic potential. Western blot analysis was used to test for the expression of CaMKII and p-CaMKII...
December 29, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28030799/resveratrol-induced-antinociception-is-involved-in-calcium-channels-and-calcium-caffeine-sensitive-pools
#19
Xiaoyu Pan, Jiechun Chen, Weijie Wang, Ling Chen, Lin Wang, Quan Ma, Jianbo Zhang, Lichao Chen, Gang Wang, Meixi Zhang, Hao Wu, Ruochuan Cheng
Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025122/protective-effect-of-rutaecarpine-against-t-bhp-induced-hepatotoxicity-by-upregulating-antioxidant-enzymes-via-the-camkii-akt-and-nrf2-are-pathways
#20
Sun Woo Jin, Yong Pil Hwang, Chul Yung Choi, Hyung Gyun Kim, Se Jong Kim, Yongan Kim, Young Chul Chung, Kyung Jin Lee, Tae Cheon Jeong, Hye Gwang Jeong
Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, has been shown to have cytoprotective potential, but the molecular mechanism underlying this activity remains unclear. Our study was designed to investigate the cytoprotective effect of rutaecarpine against tert-butyl hydroperoxide (t-BHP) and to elucidate its action mechanism of action of rutaecarpine in a cultured HepG2 cell line and in mouse liver. Rutaecarpine decreased t-BHP-induced reactive oxygen species (ROS) production, cytotoxicity, and apoptosis in HepG2 cells...
December 23, 2016: Food and Chemical Toxicology
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