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https://www.readbyqxmd.com/read/29052994/force-induced-calpain-cleavage-of-talin-is-critical-for-growth-adhesion-development-and-rigidity-sensing
#1
Mayur Saxena, Rishita Changede, James C Hone, Haguy Wolfenson, Michael P Sheetz
Cell growth depends upon formation of cell-matrix adhesions, but mechanisms detailing the transmission of signals from adhesions to control proliferation are still lacking. Here, we find that the scaffold protein talin undergoes force-induced cleavage in early adhesions to produce the talin rod fragment that is needed for cell cycle progression. Expression of non-cleavable talin blocks cell growth, adhesion maturation, proper mechanosensing, and the related property of EGF activation of motility. Further, the expression of talin rod in the presence of non-cleavable full-length talin rescues cell growth and other functions...
October 20, 2017: Nano Letters
https://www.readbyqxmd.com/read/29048243/mithramycin-a-improves-functional-recovery-by-inhibiting-bscb-disruption-and-hemorrhage-after-spinal-cord-injury
#2
Jee Youn Lee, Hye Y Choi, Chan S Park, Bong G Ju, Tae Y Yune
After spinal cord injury (SCI), blood spinal cord barrier (BSCB) disruption and progressive hemorrhage lead to secondary injury, subsequent apoptosis and/or necrosis of neuron and glia, causing permanent neurological deficits. Growing evidences indicate that mithramycin A (MA), an anticancer drug, has neuroprotective effects in ischemic brain injury and Huntington's disease. However, the precise mechanism underlying its protective effects is largely unknown. Here, we examined the effect of MA on BSCB breakdown and hemorrhage as well as subsequent inflammation after SCI...
October 19, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29019677/scalaradial-is-a-potent-inhibitor-of-transient-receptor-potential-melastatin-2-trpm2-ion-channels
#3
John G Starkus, Peter Poerzgen, Kristine Layugan, Kelly Galbraith Kawabata, Jun-Ichi Goto, Sayuri Suzuki, George Myers, Michelle Kelly, Reinhold Penner, Andrea Fleig, F David Horgen
TRPM2 is a Ca(2+)-permeable, nonselective cation channel that plays a role in oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2 inhibitors have been reported, which hampers the validation of TRPM2 as a drug target. While screening our in-house marine-derived chemical library, we identified scalaradial and 12-deacetylscalaradial as the active components within an extract of an undescribed species of Cacospongia (class Demospongiae, family Thorectidae) that strongly inhibited TRPM2-mediated Ca(2+) influx in TRPM2-overexpressing HEK293 cells...
October 11, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28906027/sur1-trpm4-and-aqp4-form-a-heteromultimeric-complex-that-amplifies-ion-water-osmotic-coupling-and-drives-astrocyte-swelling
#4
Jesse A Stokum, Min S Kwon, Seung K Woo, Orest Tsymbalyuk, Rudi Vennekens, Volodymyr Gerzanich, J Marc Simard
Astrocyte swelling occurs after central nervous system injury and contributes to brain swelling, which can increase mortality. Mechanisms proffered to explain astrocyte swelling emphasize the importance of either aquaporin-4 (AQP4), an astrocyte water channel, or of Na(+) -permeable channels, which mediate cellular osmolyte influx. However, the spatio-temporal functional interactions between AQP4 and Na(+) -permeable channels that drive swelling are poorly understood. We hypothesized that astrocyte swelling after injury is linked to an interaction between AQP4 and Na(+) -permeable channels that are newly upregulated...
September 14, 2017: Glia
https://www.readbyqxmd.com/read/28898995/uncovering-the-arrhythmogenic-potential-of-trpm4-activation-in-atrial-derived-hl-1-cells-using-novel-recording-and-numerical-approaches
#5
Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Michio Nakaya, Masayuki X Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue
Aims: Transient receptor potential cation channel subfamily melastatin member 4 (TRPM4), a Ca2+-activated nonselective cation channel abundantly expressed in the heart, has been implicated in conduction block and other arrhythmic propensities associated with cardiac remodelling and injury. The present study aimed to quantitatively evaluate the arrhythmogenic potential of TRPM4. Methods and results: Patch clamp and biochemical analyses were performed using expression system and an immortalized atrial cardiomyocyte cell line (HL-1), and numerical model simulation was employed...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28877214/direct-versus-indirect-actions-of-ghrelin-on-hypothalamic-npy-neurons
#6
Hiroshi Hashiguchi, Zhenyu Sheng, Vanessa Routh, Volodymyr Gerzanich, J Marc Simard, Joseph Bryan
OBJECTIVES: Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. MATERIALS AND METHODS: Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. RESULTS: Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices...
2017: PloS One
https://www.readbyqxmd.com/read/28876976/trpm4-activation-by-chemically-and-oxygen-deprivation-induced-ischemia-and-reperfusion-triggers-neuronal-death
#7
Elías Leiva-Salcedo, Denise Riquelme, Oscar Cerda, Andrés Stutzin
Cerebral ischemia-reperfusion injury triggers a deleterious process ending in neuronal death. This process has two components, a glutamate-dependent and a glutamate-independent mechanism. In the glutamate-independent mechanism, neurons undergo a slow depolarization eventually leading to neuronal death. However, little is known about the molecules that take part in this process. Here we show by using mice cortical neurons in culture and ischemia-reperfusion protocols that TRPM4 is fundamental for the glutamate-independent neuronal damage...
September 6, 2017: Channels
https://www.readbyqxmd.com/read/28865458/salutary-effects-of-glibenclamide-during-the-chronic-phase-of-murine-experimental-autoimmune-encephalomyelitis
#8
Volodymyr Gerzanich, Tapas K Makar, Poornachander Reddy Guda, Min Seong Kwon, Jesse A Stokum, Seung Kyoon Woo, Svetlana Ivanova, Alexander Ivanov, Rupal I Mehta, Alexandra Brooke Morris, Joseph Bryan, Christopher T Bever, J Marc Simard
BACKGROUND: In multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), inflammation is perpetuated by both infiltrating leukocytes and astrocytes. Recent work implicated SUR1-TRPM4 channels, expressed mostly by astrocytes, in murine EAE. We tested the hypothesis that pharmacological inhibition of SUR1 during the chronic phase of EAE would be beneficial. METHODS: EAE was induced in mice using myelin oligodendrocyte glycoprotein (MOG) 35-55. Glibenclamide (10 μg/day) was administered beginning 12 or 24 days later...
September 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#9
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758259/transient-receptor-potential-melastatin-4-channel-is-required-for-rat-dental-pulp-stem-cell-proliferation-and-survival
#10
T D Ngoc Tran, K E Stovall, T Suantawee, Y Hu, S Yao, L-J Yang, S Adisakwattana, H Cheng
OBJECTIVES: Investigate the role of the transient receptor potential melastatin 4 (TRPM4) channel in rat dental pulp stem cell (DPSC) proliferation and survival. MATERIALS AND METHODS: Immunofluorescence and FACS analysis were used to detect the stem cell marker CD90. Alizarin Red S and Oil Red O staining were used to identify osteoblast and adipocyte differentiation, respectively. To characterize TRPM4, patch-clamp recordings were obtained from single cells in the whole-cell configuration mode...
October 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28750076/targeted-next-generation-sequencing-detects-novel-gene-phenotype-associations-and-expands-the-mutational-spectrum-in-cardiomyopathies
#11
Cinzia Forleo, Anna Maria D'Erchia, Sandro Sorrentino, Caterina Manzari, Matteo Chiara, Massimo Iacoviello, Andrea Igoren Guaricci, Delia De Santis, Rita Leonarda Musci, Antonino La Spada, Vito Marangelli, Graziano Pesole, Stefano Favale
Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity and mortality. These diseases are genetically diverse and associated with rare mutations in a large number of genes, many of which overlap among the phenotypes. To better investigate the genetic overlap between these three phenotypes and to identify new genotype-phenotype correlations, we designed a custom gene panel consisting of 115 genes known to be associated with cardiomyopathic phenotypes and channelopathies...
2017: PloS One
https://www.readbyqxmd.com/read/28740332/a-protective-role-of-glibenclamide-in-inflammation-associated-injury
#12
REVIEW
Gensheng Zhang, Xiuhui Lin, Shufang Zhang, Huiqing Xiu, Chuli Pan, Wei Cui
Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamide's anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28644055/regulation-of-transient-receptor-potential-melastatin-4-channel-by-sarcoplasmic-reticulum-inositol-trisphosphate-receptors-role-in-human-detrusor-smooth-muscle-function
#13
Aaron Provence, Eric S Rovner, Georgi V Petkov
We recently reported key physiologic roles for Ca(2+)-activated transient receptor potential melastatin 4 (TRPM4) channels in detrusor smooth muscle (DSM). However, the Ca(2+)-signaling mechanisms governing TRPM4 channel activity in human DSM cells are unexplored. As the TRPM4 channels are activated by Ca(2+), inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the sarcoplasmic reticulum represents a potential Ca(2+) source for TRPM4 channel activation. We used clinically-characterized human DSM tissues to investigate the molecular and functional interactions of the IP3Rs and TRPM4 channels...
September 3, 2017: Channels
https://www.readbyqxmd.com/read/28614631/trpm4-regulates-akt-gsk3-%C3%AE-activity-and-enhances-%C3%AE-catenin-signaling-and-cell-proliferation-in-prostate-cancer-cells
#14
Alfredo I Sagredo, Eduardo A Sagredo, Claudio Cappelli, Pablo Báez, Andaur M Rodrigo, Constanza Blanco, Julio C Tapia, César Echeverría, Oscar Cerda, Andrés Stutzin, Felipe Simon, Katherine Marcelain, Ricardo Armisén
Increased expression of the TRPM4 channel has been reported to be associated with the progression of prostate cancer. However, the molecular mechanism underlying its effect remains unknown. This work found that decreasing TRPM4 levels leads to the reduced proliferation of PC3 cells. This effect was associated with a decrease in total β-catenin protein levels and its nuclear localization, and a significant reduction in Tcf/Lef transcriptional activity. Moreover, TRPM4 silencing increases the Ser33/Ser37/Thr41 β-catenin phosphorylated population and reduces the phosphorylation of GSK-3β at Ser9, suggesting an increase in β-catenin degradation as the underlying mechanism...
June 14, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28603015/activation-of-a-ca-2-dependent-cation-conductance-with-properties-of-trpm2-by-reactive-oxygen-species-in-lens-epithelial-cells
#15
Susanne Keckeis, Laura Wernecke, Daniel J Salchow, Nadine Reichhart, Olaf Strauß
Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca(2+)-dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca(2+)- and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca(2+)-activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells...
August 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28497254/9-phenanthrol-modulates-postinhibitory-rebound-and-afterhyperpolarizing-potentials-in-an-excitatory-motor-neuron-of-the-medicinal-leech
#16
James D Angstadt, Joshua R Giordano, Alexander J Goncalves
Postinhibitory rebound (PIR) responses in leech dorsal excitatory motor neurons (cell DE-3) are eliminated by Ca(2+) channel blockers but also exhibit a strong dependence on extracellular Na(+). These features could be explained by a voltage-gated Ca(2+) current acting in concert with a Ca(2+)-activated nonspecific current (ICAN). In vertebrates, ICAN is associated with TRPM4 channels which are blocked selectively by 9-phenanthrol. Here, we show that 9-phenanthrol selectively inhibits a late phase of PIR and simultaneously enhances afterhyperpolarizing potentials (AHPs)...
August 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/28494446/mutation-load-of-multiple-ion-channel-gene-mutations-in-brugada-syndrome
#17
Francesca Gualandi, Fatima Zaraket, Michele Malagù, Giulia Parmeggiani, Cecilia Trabanelli, Sergio Fini, Xiao Dang, Xiaoming Wei, Mingyan Fang, Matteo Bertini, Roberto Ferrari, Alessandra Ferlini
Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient...
2017: Cardiology
https://www.readbyqxmd.com/read/28475214/the-angiotensin-ii-receptor-type-1b-is-the-primary-sensor-of-intraluminal-pressure-in-cerebral-artery-smooth-muscle-cells
#18
Paulo W Pires, Eun-A Ko, Harry A T Pritchard, Michael Rudokas, Evan Yamasaki, Scott Earley
The angiotensin II receptor type 1b (AT1 Rb ) is the primary sensor of intraluminal pressure in cerebral arteries. Pressure or membrane-stretch induced stimulation of AT1 Rb activates the TRPM4 channel and results in inward transient cation currents that depolarize smooth muscle cells, leading to vasoconstriction. Activation of either AT1 Ra or AT1 Rb with angiotensin II stimulates TRPM4 currents in cerebral artery myocytes and vasoconstriction of cerebral arteries. The expression of AT1 Rb mRNA is ∼30-fold higher than AT1 Ra in whole cerebral arteries and ∼45-fold higher in isolated cerebral artery smooth muscle cells...
July 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28412320/glibenclamide-ameliorates-cerebral-edema-and-improves-outcomes-in-a-rat-model-of-status-epilepticus
#19
Zhenzhou Lin, Hua Huang, Yong Gu, Kaibin Huang, Yafang Hu, Zhong Ji, Yongming Wu, Shengnan Wang, Tingting Yang, Suyue Pan
Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders. This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group received a loading dose of 10 μg/kg of GBC, followed by 1.2 μg/6 h for 3 days, while same dose of vehicle was used as control...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28315637/trpm4-non-selective-cation-channel-variants-in-long-qt-syndrome
#20
Thomas Hof, Hui Liu, Laurent Sallé, Jean-Jacques Schott, Corinne Ducreux, Gilles Millat, Philippe Chevalier, Vincent Probst, Romain Guinamard, Patrice Bouvagnet
BACKGROUND: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterized by prolongation of the QT interval, a risk of syncope, and sudden death. There are already a number of causal genes in LQTS, but not all LQTS patients have an identified mutation, which suggests LQTS unknown genes. METHODS: A cohort of 178 LQTS patients, with no mutations in the 3 major LQTS genes (KCNQ1, KCNH2, and SCN5A), was screened for mutations in the transient potential melastatin 4 gene (TRPM4)...
March 18, 2017: BMC Medical Genetics
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