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https://www.readbyqxmd.com/read/29453416/homozygous-deletion-in-myl9-expands-the-molecular-basis-of-megacystis-microcolon-intestinal-hypoperistalsis-syndrome
#1
Carolina Araujo Moreno, Nara Sobreira, Elizabeth Pugh, Peng Zhang, Gary Steel, Fábio Rossi Torres, Denise Pontes Cavalcanti
Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disease characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition started to be defined recently, and the genes related to the syndrome (ACTG2-heterozygous variant in sporadic cases; and MYH11 (myosin heavy chain 11), LMOD1 (leiomodin 1) and MYLK (myosin light chain (MLC) kinase)-autosomal recessive inheritance), encode proteins involved in the smooth muscle contraction, supporting a myopathic basis for the disease...
February 16, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29452157/hypertrophic-cardiomyopathy-mutation-r58q-in-the-myosin-regulatory-light-chain-perturbs-thick-filament-based-regulation-in-cardiac-muscle
#2
Thomas Kampourakis, Saraswathi Ponnam, Malcolm Irving
Hypertrophic cardiomyopathy (HCM) is frequently linked to mutations in the protein components of the myosin-containing thick filaments leading to contractile dysfunction and ultimately heart failure. However, the molecular structure-function relationships that underlie these pathological effects remain largely obscure. Here we chose an example mutation (R58Q) in the myosin regulatory light chain (RLC) that is associated with a severe HCM phenotype and combined the results from a wide range of in vitro and in situ structural and functional studies on isolated protein components, myofibrils and ventricular trabeculae to create an extensive map of structure-function relationships...
February 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29452094/evolving-mechanisms-of-vascular-smooth-muscle-contraction-highlight-key-targets-in-vascular-disease
#3
REVIEW
Zhongwei Liu, Raouf A Khalil
Vascular smooth muscle (VSM) plays an important role in the regulation of vascular function. Identifying the mechanisms of VSM contraction has been a major research goal in order to determine the causes of vascular dysfunction and exaggerated vasoconstriction in vascular disease. Major discoveries over several decades have helped to better understand the mechanisms of VSM contraction. Ca 2+ has been established as a major regulator of VSM contraction, and its sources, cytosolic levels, homeostatic mechanisms and subcellular distribution have been defined...
February 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29451818/overexpression-of-heart-specific-small-subunit-of-myosin-light-chain-phosphatase-results-in-heart-failure-and-conduction-disturbance
#4
Takuro Arimura, Antoine Muchir, Masayoshi Kuwahara, Sachio Morimoto, Taisuke Ishikawa, Cheng-Kun Du, Dong-Yun Zhan, Shu Nakao, Noboru Machida, Ryo Tanaka, Yoshihisa Yamane, Takeharu Hayashi, Akinori Kimura
Mutations in genes encoding components of sarcomere cause cardiomyopathy, which is often associated with abnormal Ca 2+ sensitivity of muscle contraction. We previously showed that a heart-specific myosin light chain phosphatase small subunit, hHS-M 21 , increases the Ca 2+ -sensitivity of muscle contraction. The aim of this study was to investigate the function of hHS-M 21 in vivo and the causative role of abnormal Ca 2+ sensitivity in cardiomyopathy. We generated transgenic (Tg) mice with cardiac-specific overexpression of hHS-M 21 ...
February 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29444861/interacting-heads-motif-has-been-conserved-as-a-mechanism-of-myosin-ii-inhibition-since-before-the-origin-of-animals
#5
Kyoung Hwan Lee, Guidenn Sulbarán, Shixin Yang, Ji Young Mun, Lorenzo Alamo, Antonio Pinto, Osamu Sato, Mitsuo Ikebe, Xiong Liu, Edward D Korn, Floyd Sarsoza, Sanford I Bernstein, Raúl Padrón, Roger Craig
Electron microscope studies have shown that the switched-off state of myosin II in muscle involves intramolecular interaction between the two heads of myosin and between one head and the tail. The interaction, seen in both myosin filaments and isolated molecules, inhibits activity by blocking actin-binding and ATPase sites on myosin. This interacting-heads motif is highly conserved, occurring in invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and in myosins regulated by both Ca 2+ binding and regulatory light-chain phosphorylation...
February 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29440699/vascular-dysfunction-in-obese-diabetic-db-db-mice-involves-the-interplay-between-aldosterone-mineralocorticoid-receptor-and-rho-kinase-signaling
#6
Aurelie Nguyen Dinh Cat, Glaucia E Callera, Malou Friederich-Persson, Ana Sanchez, Maria Gabriela Dulak-Lis, Sofia Tsiropoulou, Augusto C Montezano, Ying He, Ana M Briones, Frederic Jaisser, Rhian M Touyz
Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439719/myl6b-a-myosin-light-chain-promotes-mdm2-mediated-p53-degradation-and-drives-hcc-development
#7
Xingwang Xie, Xueyan Wang, Weijia Liao, Ran Fei, Nan Wu, Xu Cong, Qian Chen, Lai Wei, Yu Wang, Hongsong Chen
BACKGROUND: Identification of novel MDM2 or p53 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways and possible treatment targets. METHODS: By means of immunoprecipitation and Mass Spectrometry analysis, we aimed to identify novel regulators of the MDM2-p53 pathway. We further clarified the impact of MYL6B on the p53 protein level and on the process of apoptosis. We also investigated the role of MYL6B in hepatocellular carcinoma by clone formation assay and by determining the correlation between its expression and prognosis of HCC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29434841/sodium-butyrate-induces-senescence-and-inhibits-the-invasiveness-of-glioblastoma-cells
#8
Hidemitsu Nakagawa, Satoru Sasagawa, Kazuyuki Itoh
Sodium butyrate (SB), a short chain (C-4) saturated fatty acid, is present in the human bowel at increased concentrations (~2 mM) as a food metabolite. It has been demonstrated that SB exerts an anti-tumor effect as a histone deacetylase inhibitor; however, its precise mechanism of action remains to be elucidated. The present study focused on the mechanisms underlying the effects of SB on glioblastoma (GB) cell proliferation, motility and invasion. In human GB A172 cells, flow cytometry and a Boyden chamber assay demonstrated that physiological concentrations of SB (0...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29428395/progesterone-induces-relaxation-of-human-umbilical-cord-vascular-smooth-muscle-cells-through-mpr%C3%AE-paqr7
#9
Yefei Pang, Peter Thomas
Progesterone effects on vascular smooth muscle cell (VSMC) relaxation and the mechanism were investigated in cultured human umbilical vein VSMCs. Membrane progesterone receptors mPRα, mPRβ, and mPRγ were highly expressed in VSMCs, whereas nuclear progesterone receptor (nPR) had low expression. Progesterone (20 nM) and 02-0 (mPR-selective agonist), but not R5020 (nPR agonist), induced muscle relaxation in both a VSMC collagen gel disk contraction assay and an endothelium-denuded human umbilical artery ring tension assay...
February 8, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29426944/incorporation-of-a-skeletal-muscle-specific-enhancer-in-the-regulatory-region-of-igf1-upregulates-igf1-expression-and-induces-skeletal-muscle-hypertrophy
#10
Yunlong Zou, Yanjun Dong, Qingyong Meng, Yaofeng Zhao, Ning Li
In this study, we upregulated insulin-like growth factor-1 (IGF1) expression specifically in skeletal muscle by engineering an enhancer into its non-coding regions and verified the expected phenotype in a mouse model. To select an appropriate site for introducing a skeletal muscle-specific myosin light chain (MLC) enhancer, three candidate sites that exhibited the least evolutionary conservation were chosen and validated in C2C12 single-cell colonies harbouring the MLC enhancer at each site. IGF1 was dramatically upregulated in only the site 2 single-cell colony series, and it exhibited functional activity leading to the formation of extra myotubes...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29410425/lymphocyte-specific-protein-1-regulates-mechanosensory-oscillation-of-podosomes-and-actin-isoform-based-actomyosin-symmetry-breaking
#11
Pasquale Cervero, Christiane Wiesner, Anais Bouissou, Renaud Poincloux, Stefan Linder
Subcellular fine-tuning of the actomyosin cytoskeleton is a prerequisite for polarized cell migration. We identify LSP (lymphocyte-specific protein) 1 as a critical regulator of actomyosin contractility in primary macrophages. LSP1 regulates adhesion and migration, including the parameters cell area and speed, and also podosome turnover, oscillation and protrusive force. LSP1 recruits myosin IIA and its regulators, including myosin light chain kinase and calmodulin, and competes with supervillin, a myosin hyperactivator, for myosin regulators, and for actin isoforms, notably β-actin...
February 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29407618/transcriptome-analysis-of-huanghai-no-2-fenneropenaeus-chinensis-response-to-wssv-using-rna-seq
#12
REVIEW
Xiaoli Shi, Xianhong Meng, Jie Kong, Sheng Luan, Kun Luo, Baoxiang Cao, Xia Lu, Xupeng Li, Baolong Chen, Jiawang Cao
White spot syndrome (WSS) is one of the most damaging phenomena in the culturing of shrimp. To characterize the mechanisms of the molecular responses to WSSV infection in 'Huanghai No. 2'' Fenneropenaeus chinensis, we used next-generation sequencing to observe the transcriptome after oral infection. A total of 108.6 million clean reads were obtained and assembled into 64,103 final unigenes with an average length of 845 bp (N50 = 1534 bp). The assembled unigenes contained 14,263 significant unigenes after BLASTX against the Nr database (E-value cut-off of 10-5)...
January 30, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29400461/conformational-ensembles-of-calmodulin-revealed-by-nonperturbing-site-specific-vibrational-probe-groups
#13
Kristen L Kelly, Shannon R Dalton, Rebecca B Wai, Kanika Ramchandani, Rosalind J Xu, Sara Linse, Casey H Londergan
Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration...
February 5, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29395909/localized-myosin-ii-activity-regulates-assembly-and-plasticity-of-the-axon-initial-segment
#14
Stephen L Berger, Alejandra Leo-Macias, Stephanie Yuen, Latika Khatri, Sylvia Pfennig, Yanqing Zhang, Esperanza Agullo-Pascual, Ghislaine Caillol, Min-Sheng Zhu, Eli Rothenberg, Carmen V Melendez-Vasquez, Mario Delmar, Christophe Leterrier, James L Salzer
The axon initial segment (AIS) is the site of action potential generation and a locus of activity-dependent homeostatic plasticity. A multimeric complex of sodium channels, linked via a cytoskeletal scaffold of ankyrin G and beta IV spectrin to submembranous actin rings, mediates these functions. The mechanisms that specify the AIS complex to the proximal axon and underlie its plasticity remain poorly understood. Here we show phosphorylated myosin light chain (pMLC), an activator of contractile myosin II, is highly enriched in the assembling and mature AIS, where it associates with actin rings...
January 25, 2018: Neuron
https://www.readbyqxmd.com/read/29378169/aberrant-endoplasmic-reticulum-stress-mediates-coronary-artery-spasm-through-regulating-mlck-mlc2-pathway
#15
Aimin Xue, Junyi Lin, Chunxing Que, Yijing Yu, Chunyan Tu, Han Chen, Baonian Liu, Xin Zhao, Tianhao Wang, Kaijun Ma, Liliang Li
Coronary artery spasm (CAS) is a pathophysiological phenomenon that may cause myocardial infarction and lead to circulatory collapse and death. Aberrant endoplasmic reticulum (ER) stress causes accumulation of misfolding proteins and has been reported to be involved in a variety of vascular diseases. The present study investigated the role of ER stress in the development of CAS and explored the possible molecular mechanisms. Initially, it was found that ER stress markers were elevated in response to drug-induced vascular smooth muscle cells (VSMCs) contraction...
January 26, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29371635/global-quantitative-proteomics-reveal-deregulation-of-cytoskeletal-and-apoptotic-signalling-proteins-in-oral-tongue-squamous-cell-carcinoma
#16
Sivagnanam Ananthi, Ch Naga Padma Lakshmi, Paul Atmika, Kumaraswamy Anbarasu, Sundarasamy Mahalingam
Oral malignancies remain to have higher morbidity and mortality rates owing to the poor understanding of the carcinogenesis and the lack of early detection and diagnosis. The lack of established biomarkers for oral tongue squamous cell carcinoma (OTSCC) resulted in aggressive multi-modality management less effective. Here, we report for the first time that a panel of potential markers identified from tongue tumor samples using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE). Our approach of combining 2D-DIGE with tandem mass spectrometry identified 24 candidate proteins including cofilins, myosin light chain family members, annexins, serpins, HSPs and tropomyosins, with significant differential expression in tongue carcinomas as compared with their matched adjacent normal tissues...
January 25, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29371201/nonmuscle-myosin-light-chain-kinase-a-key-player-in-intermittent-hypoxia-induced-vascular-alterations
#17
Claire Arnaud, Sophie Bouyon, Sylvain Recoquillon, Sandrine Brasseur, Emeline Lemarié, Anne Briançon-Marjollet, Brigitte Gonthier, Marta Toral, Gilles Faury, M Carmen Martinez, Ramaroson Andriantsitohaina, Jean-Louis Pepin
BACKGROUND: Obstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea-related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases...
January 25, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29361581/myosin-phosphorylation-improves-contractile-economy-of-mouse-fast-skeletal-muscle-during-staircase-potentiation
#18
Jordan Bunda, William Gittings, Rene Vandenboom
Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast muscle in vitro (25° C). To this end, extensor digitorum longus (EDL) muscles from Wildtype and from skMLCK devoid (skMLCK-/-) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC)...
January 4, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29361525/stress-activated-mapks-and-crm1-regulate-net1a-subcellular-localization-to-control-cell-motility-and-invasion
#19
Arzu Ulu, Wonkyung Oh, Yan Zuo, Jeffrey A Frost
The Neuroepithelial cell transforming gene 1A (Net1A) is a RhoA subfamily GEF that localizes to the nucleus in the absence of stimulation, preventing it from activating RhoA. Once relocalized in the cytosol, Net1A stimulates cell motility and extracellular matrix invasion. In the present work we investigated mechanisms responsible for Net1A cytosolic relocalization. We demonstrate that inhibition of MAPK pathways blocks Net1A relocalization, with cells being most sensitive to JNK pathway inhibition. Moreover, JNK or p38 MAPK activation is sufficient to elicit Net1A cytosolic localization...
December 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29360541/methionine-hydroxy-analogue-supplementation-modulates-gill-immunological-and-barrier-health-status-of-grass-carp-ctenopharyngodon-idella
#20
Pei Wu, Fei-Yu Pan, Lin Feng, Wei-Dan Jiang, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Yang Liu
This study was conducted to investigate the effects of methionine hydroxy analogue (MHA) on the physical barrier and immune defence in the gill of young grass carp (Ctenopharyngodon idella). A total 630 young grass carp with an average initial weight of 259.70 ± 0.47 g were fed graded levels of MHA (0, 2.4, 4.4, 6.4, 8.5 and 10.5 g/kg diet) and one DL-methionine (DLM) group (6.4 g/kg diet) for 8 weeks. After feeding trial, 15 fish from each treatment were challenged with Flavobacterium columnare...
January 19, 2018: Fish & Shellfish Immunology
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