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https://www.readbyqxmd.com/read/28437280/inhibition-of-rho-kinase-attenuates-left-ventricular-remodeling-caused-by-chronic-intermittent-hypoxia-in-rats-via-suppressing-myocardial-inflammation-and-apoptosis
#1
Zhi-Hua Wang, Die Zhu, Sheng Xie, Yan Deng, Yueying Pan, Jie Ren, Hui-Guo Liu
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. The current study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28432943/exploration-of-flexible-phenylpropylurea-scaffold-as-novel-cardiac-myosin-activators-for-the-treatment-of-systolic-heart-failure
#2
Manoj Manickam, Hitesh B Jalani, Thanigaimalai Pillaiyar, Niti Sharma, Pulla Reddy Boggu, Eeda Venkateswararao, You-Jung Lee, Eun-Seok Jeon, Sang-Hun Jung
A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81...
April 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28432261/ccm2-and-pak4-act-downstream-of-atrial-natriuretic-peptide-signaling-to-promote-cell-spreading
#3
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/28432215/actomyosin-based-tissue-folding-requires-a-multicellular-myosin-gradient
#4
Natalie C Heer, Pearson W Miller, Soline Chanet, Norbert Stoop, Jörn Dunkel, Adam C Martin
Tissue folding promotes three-dimensional (3D) form during development. In many cases, folding is associated with myosin accumulation at the apical surface of epithelial cells, as seen in the vertebrate neural tube and the Drosophila ventral furrow. This type of folding is characterized by constriction of apical cell surfaces, and the resulting cell shape change is thought to cause tissue folding. Here, we use quantitative microscopy to measure the pattern of transcription, signaling, myosin activation, and cell shape in the Drosophila mesoderm...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28432058/mk5-haplodefficiency-attenuates-hypertrophy-and-preserves-diastolic-function-during-remodeling-induced-by-chronic-pressure-overload-in-the-mouse-heart
#5
Sherin Nawaito, Dharmendra Dingar, Pramod Sahadevan, Bahira Hussein, Fatiha Sahmi, Yanfen Shi, Marc-Antoine Gillis, Matthias Gaestel, Jean-Claude Tardif, Bruce G Allen
MK5 is a protein serine and threonine kinase that is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological function(s) of MK5 remain unknown. Herein we examine the effect of MK5 haplodeficiency on cardiac function and myocardial remodeling. At 12-weeks of age, MK5 haplodeficient mice (MK5(+/-)) were smaller than age-matched wild-type litter mates (MK5(+/+)), with similar diastolic function but reduced systolic function. Transverse aortic constriction (TAC) was employed to induce a chronic pressure overload in twelve-week-old male MK5(+/-) and MK5(+/+) mice...
April 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#6
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28431393/loss-of-tpm4-1-leads-to-disruption-of-cell-cell-adhesions-and-invasive-behavior-in-breast-epithelial-cells-via-increased-rac1-signaling
#7
SukYeong Jeong, SunYoung Lim, Galina Schevzov, Peter W Gunning, David M Helfman
Here we report the identification and characterization of a novel high molecular weight isoform of tropomyosin, Tpm4.1, expressed from the human TPM4 gene. Tpm4.1 expression is down-regulated in a subset of breast cancer cells compared with untransformed MCF10A breast epithelial cells and in highly metastatic breast cancer cell lines derived from poorly metastatic MDA-MD-231 cells. In addition, patients with invasive ductal breast carcinoma show decreased TPM4 expression compared with patients with ductal breast carcinoma in situ, and low TPM4 expression is associated with poor prognosis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430047/arf-gaps-and-molecular-motors
#8
Ruibai Luo, Christine E Reed, Jeffrey A Sload, Linda Wordeman, Paul A Randazzo, Pei-Wen Chen
Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation...
April 21, 2017: Small GTPases
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
#9
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
#10
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
#11
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
#12
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/28423519/vitamin-d-and-vdr-in-cancer-cachexia-and-muscle-regeneration
#13
Andrea Camperi, Fabrizio Pin, Domiziana Costamagna, Fabio Penna, Maria Lopez Menduina, Zaira Aversa, Teresa Zimmers, Roberto Verzaro, Raffaella Fittipaldi, Giuseppina Caretti, Francesco Maria Baccino, Maurizio Muscaritoli, Paola Costelli
Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423017/auxotonic-to-isometric-contraction-transitioning-in-a-beating-heart-causes-myosin-step-size-to-down-shift
#14
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/28417963/loop-diuretics-affect-skeletal-myoblast-differentiation-and-exercise-induced-muscle-hypertrophy
#15
Shintaro Mandai, Susumu Furukawa, Manami Kodaka, Yutaka Hata, Takayasu Mori, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Daiei Takahashi, Yuki Yoshizaki, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Yasuro Furuichi, Nobuharu L Fujii, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28412087/pregestational-type-2-diabetes-mellitus-induces-cardiac-hypertrophy-in-the-murine-embryo-through-cardiac-remodeling-and-fibrosis
#16
Xue Lin, Penghua Yang, E Albert Reece, Peixin Yang
BACKGROUND: Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Experimental evidence has implied that pregnant women with T2DM and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study has revealed that maternal T2DM induces structural heart defects in their offspring. OBJECTIVE: The present study aims to determine whether maternal T2DM induces embryonic heart hypertrophy in a murine model of diabetic embryopathy...
April 12, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28411859/cd14-plays-a-protective-role-in-experimental-inflammatory-bowel-disease-by-enhancing-intestinal-barrier-function
#17
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
https://www.readbyqxmd.com/read/28411398/bud-detachment-in-hydra-requires-activation-of-fgfr-and-a-rho-rock-myosin-ii-signaling-pathway-to-ensure-formation-of-a-basal-constriction
#18
Oliver Holz, David Apel, Patrick Steinmetz, Ellen Lange, Simon Hopfenmüller, Kerstin Ohler, Stefanie Sudhop, Monika Hassel
BACKGROUND: Hydra propagates asexually by exporting tissue into a bud, which detaches four days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto- and endodermal epithelia is unknown. RESULTS: Histological sections and staining of F-actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells...
April 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28410370/a-systematic-screen-for-morphological-abnormalities-during-fission-yeast-sexual-reproduction-identifies-a-mechanism-of-actin-aster-formation-for-cell-fusion
#19
Omaya Dudin, Laura Merlini, Felipe O Bendezú, Raphaël Groux, Vincent Vincenzetti, Sophie G Martin
In non-motile fungi, sexual reproduction relies on strong morphogenetic changes in response to pheromone signaling. We report here on a systematic screen for morphological abnormalities of the mating process in fission yeast Schizosaccharomyces pombe. We derived a homothallic (self-fertile) collection of viable deletions, which, upon visual screening, revealed a plethora of phenotypes affecting all stages of the mating process, including cell polarization, cell fusion and sporulation. Cell fusion relies on the formation of the fusion focus, an aster-like F-actin structure that is marked by strong local accumulation of the myosin V Myo52, which concentrates secretion at the fusion site...
April 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28409282/motor-neuron-vulnerability-and-resistance-in-amyotrophic-lateral-sclerosis
#20
REVIEW
Jik Nijssen, Laura H Comley, Eva Hedlund
In the fatal disease-amyotrophic lateral sclerosis (ALS)-upper (corticospinal) motor neurons (MNs) and lower somatic MNs, which innervate voluntary muscles, degenerate. Importantly, certain lower MN subgroups are relatively resistant to degeneration, even though pathogenic proteins are typically ubiquitously expressed. Ocular MNs (OMNs), including the oculomotor, trochlear and abducens nuclei (CNIII, IV and VI), which regulate eye movement, persist throughout the disease. Consequently, eye-tracking devices are used to enable paralysed ALS patients (who can no longer speak) to communicate...
April 13, 2017: Acta Neuropathologica
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