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https://www.readbyqxmd.com/read/28225609/regulation-and-plasticity-of-catalysis-in-enzymes-insights-from-analysis-of-mechanochemical-coupling-in-myosin
#1
Xiya Lu, Victor Ovchinnikov, Darren Demapan, Daniel Roston, Qiang Cui
The mechanism of ATP hydrolysis in the myosin motor domain is analyzed using a combination of DFTB3/CHARMM simulations and enhanced sampling techniques. The motor domain is modeled in the pre-powerstroke state, in the post-rigor state, and a hybrid model based on the post-rigor state with a closed nucleotide-binding pocket. The ATP hydrolysis activity is found to depend on the positioning of nearby water molecules, and a network of polar residues facilitates proton transfer and charge redistribution during hydrolysis...
February 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28225074/the-wasp-arp2-3-complex-signal-cascade-is-involved-in-actin-dependent-sperm-nuclei-migration-during-double-fertilization-in-tobacco-and-maize
#2
Xiongbo Peng, Tingting Yan, Mengxiang Sun
Sperm nuclear migration during fertilization in Arabidopsis and rice has recently been found to be actin-dependent, but the driving force behind this actin cytoskeleton-dependent motion is unclear. Here, we confirmed that the actin-dependent sperm nuclei migration during fertilization is a conserved mechanism in plants. Using in vitro fertilization systems, we showed that a functional actin is also essential in maize and tobacco for sperm nuclei migration after gamete membrane fusion. Cytoskeleton depolymerization inhibitor treatments supported the view that sperm nuclei migration is actin-dependent but microtubule-independent in both egg cell and central cell during double fertilization...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224701/pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies-in-necrotizing-myopathies-myofiber-atrophy-and-impairment-of-muscle-regeneration-in-necrotizing-autoimmune-myopathies
#3
Louiza Arouche-Delaperche, Yves Allenbach, Damien Amelin, Corinna Preusse, Vincent Mouly, Wladimir Mauhin, Gaelle Dzangue Tchoupou, Laurent Drouot, Olivier Boyer, Werner Stenzel, Gillian Butler-Browne, Olivier Benveniste
OBJECTIVE: Immune mediated necrotizing myopathies (IMNM) may be associated with either anti-SRP or anti-HMGCR antibodies (Abs) and the titer of these Abs is correlated with the disease activity. We investigated if anti-SRP and anti-HMGCR Abs could be involved in muscle damages. METHODS: Muscle biopsies of patients were analyzed for atrophy and regeneration, by measuring the fibers size and by performing immunostaining of neonatal myosin heavy chain. To further understand the role of the Abs in the pathology, we performed muscle cell co-culture with the Abs...
February 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28223540/akirin2-promotes-slow-myosin-heavy-chain-expression-by-can-nfatc1-signaling-in-porcine-skeletal-muscle-satellite-cells
#4
Xiaoling Chen, Yanliu Luo, Zhiqing Huang, Guangmang Liu, Hua Zhao
The objective of this study was to evaluate the effect of Akirin2 on slow myosin heavy chain (slow MyHC, MyHC I) gene expression and its molecular mechanisms. In this study, we showed that the protein expression of Akirin2 in pig slow oxidative Psoas major muscle is higher than that in fast glycolytic tibialis anterior muscle, suggesting that Akirin2 may play a role in myofiber typing. Knockdown of Akirin2 decreased the MyHC I expression and the calcineurin (CaN) activity, and also decreased the expressions of NFATc1 and MCIP1...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223517/heart-failure-drug-changes-the-mechanoenzymology-of-the-cardiac-myosin-powerstroke
#5
John A Rohde, David D Thomas, Joseph M Muretta
Omecamtiv mecarbil (OM), a putative heart failure therapeutic, increases cardiac contractility. We hypothesize that it does this by changing the structural kinetics of the myosin powerstroke. We tested this directly by performing transient time-resolved FRET on a ventricular cardiac myosin biosensor. Our results demonstrate that OM stabilizes myosin's prepowerstroke structural state, supporting previous measurements showing that the drug shifts the equilibrium constant for myosin-catalyzed ATP hydrolysis toward the posthydrolysis biochemical state...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223172/a-simple-model-of-cardiac-muscle-for-multiscale-simulation-passive-mechanics-crossbridge-kinetics-and-calcium-regulation
#6
Fyodor A Syomin, Andrey K Tsaturyan
A simple model of cardiac muscle was designed for multiscale simulation of heart mechanics. Relaxed cardiac muscle was described as a transversally isotropic hyperelastic material. Active tension caused by actin-myosin crossbridges depends on the ensemble averaged strain of myosin heads bound to actin. Calcium activation was modeled by Ca(2+) binding to troponin-C. To account for the dependence of troponin affinity for Ca(2+) on myosin heads strongly bound to actin, the kinetics of troponin binding to Ca(2+) in the overlap zone of the thin and thick filaments and outside it were separated...
February 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28223068/parasite-control-and-skeletal-myositis-in-trypanosoma-cruzi-infected-and-exercised-rats
#7
Rômulo D Novaes, Reggiani V Gonçalves, Arlete R Penitente, Marli C Cupertino, Izabel R S C Maldonado, André Talvani, Antônio J Natali
Non-pharmacological strategies have been rarely described in the treatment of infectious diseases. Although exercise training has been recently incorporated in the clinical management of Chagas disease, the rationale basis that supports this indication is poorly understood. Thus, we investigated the effect of an aerobic exercise on the parasitism, inflammation and oxidative tissue damage in a murine model of Trypanosoma cruzi-induced skeletal myositis. Wistar rats were randomized into four groups: trained not infected (TNI) and infected (TI), sedentary not infected (SNI) and infected (SI)...
February 18, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28221712/discovery-of-myh14-as-an-important-and-unique-deafness-gene-causing-prelingually-severe-autosomal-dominant-non-syndromic-hearing-loss
#8
Bong Jik Kim, Ah Reum Kim, Jin Hee Han, Chung Lee, Doo Yi Oh, Byung Yoon Choi
BACKGROUND: Pathogenic variants of MYH14 have been known to be associated-in either a syndromic or non-syndromic manner-with hearing loss. Interestingly, all reported cases to date of MYH14-related non-syndromic hearing loss with detailed phenotypes have demonstrated mild-to-moderate progressive hearing loss with postlingual onset. METHODS: In this study, targeted resequencing (TRS) of known deafness genes was performed to identify the causative variant in two multiplex families segregating AD inherited hearing loss...
February 21, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28220794/flucrypyrim-a-novel-uterine-relaxant-has-antinociceptive-and-anti-inflammatory-effects-in-vivo
#9
Zhongtang Li, Limei Wang, Yue Cong, Lin Guo, Xiaohui Lin, Zuyin Yu, Xingan Wu, Junxing Dong, Rifang Yang, Yuwen Cong
Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220174/discovery-of-s-3-hydroxyblebbistatin-and-s-3-aminoblebbistatin-polar-myosin-ii-inhibitors-with-superior-research-tool-properties
#10
Sigrid Verhasselt, Bart I Roman, Olivier De Wever, Kristof Van Hecke, Rik Van Deun, Marc E Bracke, Christian V Stevens
In search of myosin II inhibitors with superior research tool properties, a chemical optimization campaign of the blebbistatin scaffold was conducted in this paper. (S)-Blebbistatin is the best known small-molecule inhibitor of myosin II ATPase activity. Unfortunately, as a research tool this compound has several deficiencies: it is photolabile and (photo)toxic, has low water solubility, and its (fluorescent) precipitates interfere in (fluorescence) readouts. In view of obtaining tool compounds with improved properties, both enantiomers of a series of D-ring modified polar analogs were prepared...
February 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28217409/muscle-derived-stem-cells-stimulate-muscle-myofiber-repair-and-counteract-fat-infiltration-in-a-diabetic-mouse-model-of-critical-limb-ischemia
#11
J Tsao, I Kovanecz, N Awadalla, R Gelfand, I Sinha-Hikim, R A White, N F Gonzalez-Cadavid
BACKGROUND: Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D...
December 2016: Journal of Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28216317/tropomyosin-isoforms-specify-functionally-distinct-actin-filament-populations-in%C3%A2-vitro
#12
Gergana Gateva, Elena Kremneva, Theresia Reindl, Tommi Kotila, Konstantin Kogan, Laurène Gressin, Peter W Gunning, Dietmar J Manstein, Alphée Michelot, Pekka Lappalainen
Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins, including actin-depolymerizing factor (ADF)/cofilins and myosins, with actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes. Different isoforms display non-redundant functions and partially non-overlapping localization patterns, for example within the stress fiber network [6, 7]...
February 14, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28215905/apobec2-negatively-regulates-myoblast-differentiation-in-muscle-regeneration
#13
Hideaki Ohtsubo, Yusuke Sato, Takahiro Suzuki, Wataru Mizunoya, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi
Recently we found that the deficiency of APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, leads to a diminished muscle mass and increased myofiber with centrally-located nuclei known as dystrophic phenotypes. APOBEC2 expression is predominant in skeletal and cardiac muscles and elevated exclusively at the early-differentiation phase of wild-type (WT) myoblast cultures; however the physiological significance is still un-known. Here we show that APOBEC2 is a key negative regulator of myoblast differentiation in muscle regeneration...
February 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28214569/effect-of-testosterone-on-the-phenotypic-modulation-of-corpus-cavernosum-smooth-muscle-cells-in-a-castrated-rat-model
#14
Luhao Liu, Ermao Li, Futian Li, Lianmin Luo, Shankun Zhao, Ran Kang, Jintai Luo, Zhigang Zhao
OBJECTIVE: To investigate the effect of testosterone (T) on the phenotypic modulation of corpus cavernosum smooth muscle (CCSM) cells in a castrated rat model. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups: control group, castration group, and castration with testosterone supplementation (castration+T) group. Erectile function, histological change and biochemical markers were assessed for phenotypic modulation of CCSM cells in corporal tissue...
February 15, 2017: Urology
https://www.readbyqxmd.com/read/28214291/segmental-distribution-of-myosin-heavy-chain-isoforms-within-single-muscle-fibers
#15
Ming Zhang, Maree Gould
Despite many studies looking at the distribution of myosin heavy chain (MHC) isoforms across a transverse section of muscle, knowledge of MHC distribution along the longitudinal axis of a single skeletal muscle fiber has been relatively overlooked. Immunocytochemistry was performed on serial sections of rat extensor digitorum longus (EDL) muscle to identify MHC types I, IIA, IIX, IIY and IIB. Sixteen fascicles which contained a total of 362 fibers were randomly and systematically sampled from the 3 EDL muscles...
February 18, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28214148/muscle-characteristics-only-partially-explain-color-variations-in-fresh-hams
#16
K Stufft, J Elgin, B Patterson, S K Matarneh, R Preisser, H Shi, E M England, T L Scheffler, E W Mills, D E Gerrard
Fresh hams display significant lean color variation that persists through further processing and contributes to a less desirable cured product. In an attempt to understand the underlying cause of this color disparity, we evaluated the differences in muscle characteristics and energy metabolites across semimembranosus (SM) muscles differing in color variation. The L* (lightness) and a* (redness) values were highest and lowest (P<0.001), respectfully in the most caudal aspects of the muscle while the ultimate pH was the lowest (P<0...
December 24, 2016: Meat Science
https://www.readbyqxmd.com/read/28213770/myosin-heavy-chain-and-cardiac-troponin-t-damage-is-associated-with-impaired-myofibrillar-atpase-activity-contributing-to-sarcomeric-dysfunction-in-ca-2-paradox-rat-hearts
#17
Árpád Kovács, Judit Kalász, Enikő T Pásztor, Attila Tóth, Zoltán Papp, Naranjan S Dhalla, Judit Barta
This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca(2+)-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca(2+)-depletion, and then Ca(2+)-repletion after Ca(2+)-depletion (Ca(2+)-paradox) by Langendorff method. During heart perfusion left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of pressure development (+ dP/dt), and pressure decay (-dP/dt) were registered. Control LVDP (127...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28212802/smooth-muscle-phenotypic-diversity-effect-on-vascular-function-and-drug-responses
#18
S A Fisher
At its simplest resistance to blood flow is regulated by changes in the state of contraction of the vascular smooth muscle (VSM), a function of the competing activities of the myosin kinase and phosphatase determining the phosphorylation and activity of the myosin ATPase motor protein. In contrast, the vascular system of humans and other mammals is incredibly complex and highly regulated. Much of this complexity derives from phenotypic diversity within the smooth muscle, reflected in very differing power outputs and responses to signaling pathways that regulate vessel tone, presumably having evolved over the millennia to optimize vascular function and its control...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212799/rho-mancing-to-sensitize-calcium-signaling-for-contraction-in-the-vasculature-role-of-rho-kinase
#19
T Szasz, R C Webb
Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212798/protein-kinase-c-as-regulator-of-vascular-smooth-muscle-function-and-potential-target-in-vascular-disorders
#20
H C Ringvold, R A Khalil
Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca(2+)-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca(2+)-dependent α, β, and γ, novel Ca(2+)-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs...
2017: Advances in Pharmacology
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