scholarly journals Regulation of Myosin Light-Chain Phosphatase Activity to Generate Airway Smooth Muscle Hypercontractility

2020 ◽  
Vol 11 ◽  
Author(s):  
Mayra D. Álvarez-Santos ◽  
Marisol Álvarez-González ◽  
Samuel Estrada-Soto ◽  
Blanca Bazán-Perkins
Keyword(s):  
Smooth Muscle ◽  
Phosphatase Activity ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphatase

Mechanical strain increases contractile enzyme activity in cultured airway smooth muscle cells

1995 ◽  
Vol 268 (6) ◽  
pp. L999-L1005 ◽  
Author(s):  
P. G. Smith ◽  
T. Tokui ◽  
M. Ikebe
Keyword(s):  
Smooth Muscle ◽  
Atpase Activity ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Mechanical Strain ◽  
Physical Stress ◽  
Airway Smooth Muscle Cells ◽  
Myosin Light Chain Phosphatase ◽  
Actomyosin Atpase

Smooth muscle hypertrophy is often found in tissue subjected to abnormal physical stress. To determine if physical stress (strain) per se could increase the contractile potential of airway smooth muscle (ASM), we compared cultured ASM cells subjected to strain to control cells (no strain) for rates of 1) myosin light chain kinase (MLCK)-mediated myosin light chain (LC20) phosphorylation, 2) actin-activated myosin ATPase, and 3) myosin light chain phosphatase-mediated myosin dephosphorylation. Lysates from strained cells showed increases in both LC20 phosphorylation activity and actomyosin ATPase activity but decreased rates of phosphatase-dependent myosin dephosphorylation. The increased LC20 phosphorylation activity and ATPase activity of the strained cells were accompanied by increases in cellular content of MLCK and myosin, respectively, compared with control. Because the cultured ASM cells exposed to strain expressed higher MLCK activity and actomyosin ATPase activity but lower myosin light chain phosphatase activity, these data suggest that physical stress in part determines ASM potential for contractile state.

scholarly journals Regions of the 110-kDa Regulatory Subunit M110 Required for Regulation of Myosin-Light-Chain-Phosphatase Activity in Smooth Muscle

1996 ◽  
Vol 239 (2) ◽  
pp. 326-332 ◽  
Author(s):  
Philippe Gailly ◽  
Xuqiong Wu ◽  
Timothy A. J. Haystead ◽  
Andrew P. Somlyo ◽  
Patricia T. W. Cohen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Phosphatase Activity ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Regulatory Subunit ◽  
Myosin Light Chain Phosphatase

Calcium Sensitization in Smooth Muscle Involving Regulation of Myosin Light Chain Phosphatase Activity

2018 ◽  
pp. 123-153 ◽  
Author(s):  
Justin A. MacDonald ◽  
Michael P. Walsh ◽  
William C. Cole
Keyword(s):  
Smooth Muscle ◽  
Phosphatase Activity ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphatase ◽  
Calcium Sensitization

Myosin light chain phosphatase activity in ragweed pollen-sensitized canine tracheal smooth muscle.

1994 ◽  
Vol 11 (6) ◽  
pp. 676-681 ◽  
Author(s):  
X Liu ◽  
A J Halayko ◽  
G Liu ◽  
K Rao ◽  
H Jiang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Phosphatase Activity ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Ragweed Pollen ◽  
Tracheal Smooth Muscle ◽  
Myosin Light Chain Phosphatase

scholarly journals Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium.

1992 ◽  
Vol 267 (30) ◽  
pp. 21492-21498
Author(s):  
M.C. Gong ◽  
A Fuglsang ◽  
D Alessi ◽  
S Kobayashi ◽  
P Cohen ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphatase

scholarly journals FFAR1 activation attenuates histamine-induced myosin light chain phosphorylation and cortical tension development in human airway smooth muscle cells

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Shengjie Xu ◽  
Anthony Schwab ◽  
Nikhil Karmacharya ◽  
Gaoyuan Cao ◽  
Joanna Woo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Airway Hyperreactivity ◽  
Human Airway Smooth Muscle ◽  
Tension Development ◽  
Cortical Tension ◽  
Human Airway ◽  
Mlc Phosphorylation

Abstract Background Activation of free fatty acid receptors (FFAR1 and FFAR4) which are G protein-coupled receptors (GPCRs) with established (patho)physiological roles in a variety of obesity-related disorders, induce human airway smooth muscle (HASM) cell proliferation and shortening. We reported amplified agonist-induced cell shortening in HASM cells obtained from obese lung donors. We hypothesized that FFAR1 modulate excitation–contraction (EC) coupling in HASM cells and play a role in obesity-associated airway hyperresponsiveness. Methods In HASM cells pre-treated (30 min) with FFAR1 agonists TAK875 and GW9508, we measured histamine-induced Ca2+ mobilization, myosin light chain (MLC) phosphorylation, and cortical tension development with magnetic twisting cytometry (MTC). Phosphorylation of MLC phosphatase and Akt also were determined in the presence of the FFAR1 agonists or vehicle. In addition, the effects of TAK875 on MLC phosphorylation were measured in HASM cells desensitized to β2AR agonists by overnight salmeterol treatment. The inhibitory effect of TAK875 on MLC phosphorylation was compared between HASM cells from age and sex-matched non-obese and obese human lung donors. The mean measurements were compared using One-Way ANOVA with Dunnett’s test for multiple group comparisons or Student’s t-test two-group comparison. For cortical tension measurements by magnetic twisted cytometry, mixed effect model using SAS V.9.2 was applied. Means were considered significant when p ≤ 0.05. Results Unexpectedly, we found that TAK875, a synthetic FFAR1 agonist, attenuated histamine-induced MLC phosphorylation and cortical tension development in HASM cells. These physiological outcomes were unassociated with changes in histamine-evoked Ca2+ flux, protein kinase B (AKT) activation, or MLC phosphatase inhibition. Of note, TAK875-mediated inhibition of MLC phosphorylation was maintained in β2AR-desensitized HASM cells and across obese and non-obese donor-derived HASM cells. Conclusions Taken together, our findings identified the FFAR1 agonist TAK875 as a novel bronchoprotective agent that warrants further investigation to treat difficult-to-control asthma and/or airway hyperreactivity in obesity.

Mechanical strain increases velocity and extent of shortening in cultured airway smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. L343-L348 ◽  
Author(s):  
Paul G. Smith ◽  
Chaity Roy ◽  
Jamie Dreger ◽  
Frank Brozovich
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Mechanical Strain ◽  
Airway Smooth Muscle Cells ◽  
Maximal Velocity ◽  
Cell Contractility ◽  
Cell Shortening

Abnormal mechanical stress on lung tissue is associated with increased mass and contractility of airway smooth muscle (ASM). We have reported that cultured ASM cells subjected to cyclic strain exhibit increased myosin light chain kinase (MLCK) and stress filaments. Increased MLCK may increase contractile velocity, whereas increased stress filaments could impede cell shortening by increasing the cell’s internal load. To study strain-induced changes in cell contractility, the time course of shortening of individual cells exposed to 90 mM KCl was recorded. Length vs. time plots revealed significantly greater maximal velocity of shortening in strain cells than control (no strain). This correlated with an increase in MLCK and myosin light chain phosphorylation measured in strain cells in separate experiments. The extent of cell shortening tended to be greater in the strain cells so that increased impedance to shortening was not detected. Mechanical stress may therefore increase the contractility of ASM by increasing the content of MLCK.

Isotonic relaxation of control and sensitized airway smooth muscle

2005 ◽  
Vol 83 (10) ◽  
pp. 941-951 ◽  
Author(s):  
N L Stephens ◽  
A Fust ◽  
H Jiang ◽  
W Li ◽  
X Ma
Keyword(s):  
Smooth Muscle ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Phase Iii ◽  
Contractile Element ◽  
Second Phase ◽  
Half Time ◽  
Phase Phase

Smooth muscle relaxation has most often been studied in isometric mode. However, this only tells us about the stiffness properties of the bronchial wall and thus only about wall capacitative properties. It tells us little about airflow. To study the latter, which of course is the meaningful parameter in regulation of ventilation and in asthma, we studied isotonic shortening of bronchial smooth muscle (BSM) strips. Failure of BSM to relax could be another important factor in maintaining high airway resistance. To analyze relaxation curves, we developed an index of isotonic relaxation, t1/2(P, lCE), which is the half-time for relaxation that is independent of muscle load (P) and of initial contractile element length (lCE). This index was measured in curves of relaxation initiated at 2 s (normally cycling crossbridges) and at 10 s (latch-bridges). At 10 s no difference was seen for adjusted t1/2(P, lCE) between curves obtained from control and sensitized BSM, (8.38 ± 0.92 s vs. 7.78 ± 0.93 s, respectively). At 2 s the half-time was almost doubled in the sensitized BSM (6.98 ± 0.01 s (control) vs. 12.74 ± 2.5 s (sensitized)). Thus, changes in isotonic relaxation are only seen during early contraction. Using zero load clamps, we monitored the time course of velocity during relaxation and noted that it varied according to 3 phases. The first phase (phase i) immediately followed cessation of electrical field stimulation (EFS) at 10 s and showed almost the same velocity as during the latter 1/3 of shortening; the second phase (phase ii) was linear in shape and is associated with zero load velocity, we speculate it could stem from elastic recoil of the cells' internal resistor; and the third phase (phase iii) was convex downwards. The zero load velocities in phase iii showed a surprising spontaneous increase suggesting reactivation of the muscle. Measurements of intracellular calcium (Fura-2 study) and of phosphorylation of the 20 kDa myosin light chain showed simultaneous increments, indicating phase iii represented an active process. Studies are under way to determine what changes occur in these 3 phases in a sensitized muscle. And of course, in the context of this conference, just what role the plastic properties of the muscle play in relaxation requires serious consideration.Key words: airway smooth muscle, sensitized smooth muscle, isotonic relaxation, intracellular calcium transients, myosin light chain (20 kDa) phosphorylation.

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