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https://www.readbyqxmd.com/read/28520587/complementary-roles-of-nod2-in-hematopoietic-and-nonhematopoietic-cells-in-preventing-gut-barrier-dysfunction-dependent-on-mlck-activity
#1
Ziad Al Nabhani, Nicolas Montcuquet, Maryline Roy, Monique Dussaillant, Jean-Pierre Hugot, Frédérick Barreau
BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability...
May 16, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28510043/pseudophosphorylation-of-cardiac-myosin-regulatory-light-chain-a-promising-new-tool-for-treatment-of-cardiomyopathy
#2
REVIEW
Sunil Yadav, Danuta Szczesna-Cordary
Many genetic mutations in sarcomeric proteins, including the cardiac myosin regulatory light chain (RLC) encoded by the MYL2 gene, have been implicated in familial cardiomyopathies. Yet, the molecular mechanisms by which these mutant proteins regulate cardiac muscle mechanics in health and disease remain poorly understood. Evidence has been accumulating that RLC phosphorylation has an influential role in striated muscle contraction and, in addition to the conventional modulation via Ca(2+) binding to troponin C, it can regulate cardiac muscle function...
February 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#3
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28493278/the-bicellular-tensile-force-sorts-the-localization-of-lsrs-in-bicellular-and-tricellular-junctions
#4
Takayuki Kohno, Shin Kikuchi, Takafumi Ninomiya, Takashi Kojima
Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight junctions. Recent studies have shown that changes in the localization and expression profiles of LSRs are associated with malignancy of endometrial carcinomas, although the precise mechanisms by which malignant progression induces changes in the localization of LSRs are still unknown. In this study, we found that changes in cell tension correlated with alterations in the junctional localization of LSRs in endometrial cancer Sawano cells...
May 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28488585/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#5
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485676/assessment-of-preclinical-liver-and-skeletal-muscle-biomarkers-following-clofibrate-administration-in-wistar-rats
#6
Pierre Maliver, Matthias Festag, Moritz Bennecke, Francois Christen, Balázs Bánfai, Barbara Lenz, Michael Winter
Clofibrate is a known rodent hepatotoxicant classically associated with hepatocellular hypertrophy and increased serum activities of cellular alanine aminotransferase/aspartate aminotransferase (ALT/AST) in the absence of microscopic hepatocellular degeneration. At toxic dose, clofibrate induces liver and skeletal muscle injury. The objective of this study was to assess novel liver and skeletal muscle biomarkers following clofibrate administration in Wistar rats at different dose levels for 7 days. In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28484504/effect-of-qskl-on-mapk-and-rhoa-pathways-in-a-rat-model-of-heart-failure
#7
Kai Xia, Qiyan Wang, Chun Li, Zifan Zeng, Yong Wang, Wei Wang
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28484126/mechanisms-underlying-the-pathogenesis-of-hyper-contractility-of-bronchial-smooth-muscle-in-allergic-asthma
#8
Hiroyasu Sakai, Wataru Suto, Yuki Kai, Yoshihiko Chiba
Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca(2+)-mediated phosphorylation of myosin light chain (MLC), contractile agonists also enhance MLC phosphorylation level, Ca(2+)-independently, by inactivating MLC phosphatase (MLCP), called Ca(2+) sensitization of contraction, in smooth muscle cells including airways...
2017: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
https://www.readbyqxmd.com/read/28475612/calmodulin-like-proteins-localized-to-the-conoid-regulate-motility-and-cell-invasion-by-toxoplasma-gondii
#9
Shaojun Long, Kevin M Brown, Lisa L Drewry, Bryan Anthony, Isabelle Q H Phan, L David Sibley
Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth...
May 5, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28472054/a-mathematical-model-coupling-polarity-signaling-to-cell-adhesion-explains-diverse-cell-migration-patterns
#10
William R Holmes, JinSeok Park, Andre Levchenko, Leah Edelstein-Keshet
Protrusion and retraction of lamellipodia are common features of eukaryotic cell motility. As a cell migrates through its extracellular matrix (ECM), lamellipod growth increases cell-ECM contact area and enhances engagement of integrin receptors, locally amplifying ECM input to internal signaling cascades. In contrast, contraction of lamellipodia results in reduced integrin engagement that dampens the level of ECM-induced signaling. These changes in cell shape are both influenced by, and feed back onto ECM signaling...
May 4, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28467684/cardiac-contractility-motor-function-and-cross-bridge-kinetics-in-n47k-rlc-mutant-mice
#11
Li Wang, Katarzyna Kazmierczak, Chen-Ching Yuan, Sunil Yadav, Masataka Kawai, Danuta Szczesna-Cordary
We have investigated the physiology and mechanical profiles of skinned papillary muscle fibers from transgenic mice expressing the N47K mutation in the myosin regulatory light chain (RLC), shown to cause hypertrophic cardiomyopathy in humans. The results were compared with wild-type (WT) mice, both expressing the human ventricular RLC. Rate constants of a cross-bridge (XB) cycle were deduced from tension transients induced by sinusoidal length changes during maximal Ca(2+) activation, and were studied as a function of MgATP, MgADP, and Pi concentrations...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28455503/lamins-and-nesprin-1-mediate-inside-out-mechanical-coupling-in-muscle-cell-precursors-through-fhod1
#12
Christine Schwartz, Martina Fischer, Kamel Mamchaoui, Anne Bigot, Thevy Lok, Claude Verdier, Alain Duperray, Richard Michel, Ian Holt, Thomas Voit, Suzanna Quijano-Roy, Gisèle Bonne, Catherine Coirault
LINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28452077/structure-and-function-of-human-muscle-fibres-and-muscle-proteome-in-physically-active-older-men
#13
Lorenza Brocca, Jamie S McPhee, Emanuela Longa, Monica Canepari, Olivier Seynnes, Giuseppe De Vito, Maria Antonietta Pellegrino, Marco Narici, Roberto Bottinelli
Contradictory results have been reported on the impact of ageing on structure and functions of skeletal muscle fibres likely due to complex interplay between ageing and other phenomena such as disuse and diseases. Here we recruited healthy, physically and socially active young (YO) and elderly (EL) men in order to study aging per se without the confounding effects of impaired physical function. In vivo analyses of quadriceps and in vitro analyses of vastus lateralis muscle biopsies were performed. In EL subjects, our results show that: (i) quadriceps volume, maximum voluntary torque (MVC), and patellar tendon force (Ft) were significantly lower; (ii) muscle fibres went through significant atrophy and impairment of specific force (Po/CSA) and unloaded shortening velocity (Vo); (iii) myosin/actin ratio and myosin content in individual muscle fibres were not altered; (iv) muscle proteome went through quantitative adaptations, namely an up-regulation of the content of several groups of proteins among which myofibrillar proteins and antioxidant defence systems; (v) muscle proteome went through qualitative adaptations, namely phosphorylation of several proteins, including Myosin Light Chain-2 slow and Troponin T and carbonylation of Myosin Heavy Chains...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28432261/ccm2-and-pak4-act-downstream-of-atrial-natriuretic-peptide-signaling-to-promote-cell-spreading
#14
Koichi Miura, Takashi Nojiri, Yoshiharu Akitake, Koji Ando, Shigetomo Fukuhara, Masahiro Zenitani, Toru Kimura, Jun Hino, Mikiya Miyazato, Hiroshi Hosoda, Kenji Kangawa
Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated in part by endothelial cells. Both in vivo and in vitro , ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A, and used them to analyze the molecular mechanisms responsible for actin reorganization...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#15
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28427997/distinct-sequences-and-post-translational-modifications-in-cardiac-atrial-and-ventricular-myosin-light-chains-revealed-by-top-down-mass-spectrometry
#16
Zachery R Gregorich, Wenxuan Cai, Ziqing Lin, Albert J Chen, Ying Peng, Takushi Kohmoto, Ying Ge
Myosin is the principal component of the thick filaments that, through interactions with the actin thin filaments, mediates force production during muscle contraction. Myosin is a hexamer, consisting of two heavy chains, each associated with an essential (ELC) and a regulatory (RLC) light chain, which bind the lever-arm of the heavy chain and play important modulatory roles in striated muscle contraction. Nevertheless, a comprehensive assessment of the sequences of the ELC and RLC isoforms, as well as their post-translational modifications, in the heart remains lacking...
April 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28427618/effects-of-high-intensity-unltrasound-on-structural-and-physicochemical-properties-of-myosin-from-silver-carp
#17
Ru Liu, Qing Liu, Shanbai Xiong, Yicheng Fu, Liang Chen
Myosin from silver carp was sonicated with varying power output (100, 150, 200 and 250W) for 3, 6, 9, and 12min. The changes in the structure and physicochemical properties of myosin were evaluated by dynamic light scattering, SDS-PAGE and some physicochemical indexes. The ultrasound treatments induced a significant conversion of myosin aggregates to smaller ones with a more uniform distribution, and obvious enhancement in solubility. The structure of myosin was also notably changed by sonication, with a decrease in Ca(2+)-ATPase activity and SH content, and an increase in surface hydrophobicity...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28424493/regulation-of-intraocular-pressure-by-microrna-cluster-mir-143-145
#18
Xinyu Li, Fangkun Zhao, Mei Xin, Guorong Li, Coralia Luna, Guigang Li, Qinbo Zhou, Yuguang He, Bo Yu, Eric Olson, Pedro Gonzalez, Shusheng Wang
Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423017/auxotonic-to-isometric-contraction-transitioning-in-a-beating-heart-causes-myosin-step-size-to-down-shift
#19
Thomas P Burghardt, Xiaojing Sun, Yihua Wang, Katalin Ajtai
Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%...
2017: PloS One
https://www.readbyqxmd.com/read/28411859/cd14-plays-a-protective-role-in-experimental-inflammatory-bowel-disease-by-enhancing-intestinal-barrier-function
#20
Stephanie Buchheister, Manuela Buettner, Marijana Basic, Andreas Noack, Gerhard Breves, Barbara Buchen, Lydia M Keubler, Christoph Becker, André Bleich
Intestinal homeostasis disturbance through intestinal barrier disruption presumably plays a key role in inflammatory bowel disease (IBD) development. Genetic and candidate gene analyses in an Il10-deficient IBD mouse model system identified Cd14 as a potentially protective candidate gene. The role of Cd14 in colitis development was determined using dextran sulfate sodium (DSS)-induced acute and an Il10-deficiency-induced chronic model of intestinal inflammation. Intestinal permeability was investigated by fluorescein isothiocyanate-dextran uptake assay, quantitative RT-PCR analysis of tight junction proteins, myosin light chain kinase, and proinflammatory cytokine expression...
April 5, 2017: American Journal of Pathology
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