scholarly journals Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

2018 ◽  
Author(s):  
Othman Al‑Shboul ◽  
Ahmed Al‑Dwairi ◽  
Mohammad Alqudah ◽  
Ayman Mustafa
2015 ◽  
Vol 93 (6) ◽  
pp. 405-411 ◽  
Author(s):  
Othman Al-Shboul ◽  
Ayman Mustafa

Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.


2004 ◽  
Vol 286 (2) ◽  
pp. R233-R249 ◽  
Author(s):  
Julia M. Orshal ◽  
Raouf A. Khalil

The greater incidence of hypertension and coronary artery disease in men and postmenopausal women compared with premenopausal women has been related, in part, to gender differences in vascular tone and possible vascular protective effects of the female sex hormones estrogen and progesterone. However, vascular effects of the male sex hormone testosterone have also been suggested. Estrogen, progesterone, and testosterone receptors have been identified in blood vessels of human and other mammals and have been localized in the plasmalemma, cytosol, and nuclear compartments of various vascular cells, including the endothelium and the smooth muscle. The interaction of sex hormones with cytosolic/nuclear receptors triggers long-term genomic effects that could stimulate endothelial cell growth while inhibiting smooth muscle proliferation. Activation of plasmalemmal sex hormone receptors may trigger acute nongenomic responses that could stimulate endothelium-dependent mechanisms of vascular relaxation such as the nitric oxide-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Additional endothelium-independent effects of sex hormones may involve inhibition of the signaling mechanisms of vascular smooth muscle contraction such as intracellular Ca2+ concentration and protein kinase C. The sex hormone-induced stimulation of the endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms of vascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone replacement therapy during natural and surgically induced deficiencies of gonadal hormones.


2019 ◽  
Vol 317 (2) ◽  
pp. L235-L246 ◽  
Author(s):  
Ling Luo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow ◽  
Pasquale Chitano

The cyclic interaction between myosin crossbridges and actin filaments underlies smooth muscle contraction. Phosphorylation of the 20-kDa myosin light chain (MLC20) is a crucial step in activating the crossbridge cycle. Our current understanding of smooth muscle contraction is based on observed correlations among MLC20 phosphorylation, maximal shortening velocity ( Vmax), and isometric force over the time course of contraction. However, during contraction there are changes in the extent of phosphorylation of many additional proteins as well as changes in activation of enzymes associated with the signaling pathways. As a consequence, the mechanical manifestation of muscle contraction is likely to change with time. To simplify the study of these relationships, we measured the mechanical properties of airway smooth muscle at different levels of MLC20 phosphorylation at a fixed time during contraction. A simple correlation emerged when time-dependent variables were fixed. MLC20 phosphorylation was found to be directly and linearly correlated with the active stress, stiffness, and power of the muscle; the observed weak dependence of Vmax on MLC20 phosphorylation could be explained by the presence of an internal load in the muscle preparation. These results can be entirely explained by the Huxley crossbridge model. We conclude that when the influence of time-dependent events during contraction is held constant, the basic crossbridge mechanism in smooth muscle is the same as that in striated muscle.


Author(s):  
P. Virych ◽  
O. Shelyuk ◽  
V. Martynyuk ◽  
S. Chumakov

The optical system registration of smooth muscle contraction in isometric mode was developed. Testing of system on smooth muscle strips of rat stomach and caecum was performed. It was tested the possibility of recording optical system spontaneous activity of smooth muscle. The resulting muscle contractions parameters correspond to the literature. Thus designed optical-mechanical method for detecting force and speed can be used for recording isometric contractions of smooth muscles of the stomach and caecum of rats and, therefore, to study the effect of different effectors their mechanokinetic.


2021 ◽  
Vol 82 (5) ◽  
Author(s):  
Hannah J. Pybus ◽  
Amanda L. Tatler ◽  
Lowell T. Edgar ◽  
Reuben D. O’Dea ◽  
Bindi S. Brook

AbstractPrecision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.


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