The RhoA-Rho Kinase Axis Contributes To Hyperreactivity Of Airway Smooth Muscle From Allergen Naive Caveolin-1 Knockout Mice

2012 ◽  
Author(s):  
Dedmer Schaafsma ◽  
Sarah A. Maltby ◽  
Behzad Yeganeh ◽  
Sujata Basu ◽  
Karol D. McNeill ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Knockout Mice ◽  
Rho Kinase ◽  
Caveolin 1

scholarly journals Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle

2015 ◽  
Vol 308 (1) ◽  
pp. L1-L10 ◽  
Author(s):  
Bo Lan ◽  
Linhong Deng ◽  
Graham M. Donovan ◽  
Leslie Y. M. Chin ◽  
Harley T. Syyong ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Initial Phase ◽  
Rho Kinase ◽  
Myosin Filament ◽  
Second Phase ◽  
Minimal Effect ◽  
Kinase Inhibition ◽  
Myosin Filaments ◽  
Force Maintenance

Smooth muscle contraction can be divided into two phases: the initial contraction determines the amount of developed force and the second phase determines how well the force is maintained. The initial phase is primarily due to activation of actomyosin interaction and is relatively well understood, whereas the second phase remains poorly understood. Force maintenance in the sustained phase can be disrupted by strains applied to the muscle; the strain causes actomyosin cross-bridges to detach and also the cytoskeletal structure to disassemble in a process known as fluidization, for which the underlying mechanism is largely unknown. In the present study we investigated the ability of airway smooth muscle to maintain force after the initial phase of contraction. Specifically, we examined the roles of Rho-kinase and protein kinase C (PKC) in force maintenance. We found that for the same degree of initial force inhibition, Rho-kinase substantially reduced the muscle's ability to sustain force under static conditions, whereas inhibition of PKC had a minimal effect on sustaining force. Under oscillatory strain, Rho-kinase inhibition caused further decline in force, but again, PKC inhibition had a minimal effect. We also found that Rho-kinase inhibition led to a decrease in the myosin filament mass in the muscle cells, suggesting that one of the functions of Rho-kinase is to stabilize myosin filaments. The results also suggest that dissolution of myosin filaments may be one of the mechanisms underlying the phenomenon of fluidization. These findings can shed light on the mechanism underlying deep inspiration induced bronchodilation.

scholarly journals Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction

2004 ◽  
Vol 143 (4) ◽  
pp. 477-484 ◽  
Author(s):  
Dedmer Schaafsma ◽  
Reinoud Gosens ◽  
I Sophie T Bos ◽  
Herman Meurs ◽  
Johan Zaagsma ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Allergic Sensitization ◽  
Rho Kinase ◽  
Smooth Muscle Contraction

scholarly journals Caveolae from canine airway smooth muscle contain the necessary components for a role in Ca2+ handling

2000 ◽  
Vol 279 (6) ◽  
pp. L1226-L1235 ◽  
Author(s):  
Peter J. Darby ◽  
C. Y. Kwan ◽  
Edwin E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Connexin 43 ◽  
Tracheal Smooth Muscle ◽  
Specific Marker ◽  
Cell Periphery ◽  
Caveolin 1 ◽  
Cytoplasmic Face ◽  
Detergent Treatment ◽  
Trisphosphate Receptor

To explain that bronchial smooth muscle undergoes sustained agonist-induced contractions in a Ca2+-free medium, we hypothesized that caveolae in the plasma membrane (PM) contain protected Ca2+. We isolated caveolae from canine tracheal smooth muscle by detergent treatment of PM-derived microsomes. Detergent-resistant membranes were enriched in caveolin-1, a specific marker for caveolae as well as for L-type Ca2+ channels and Ca2+ binding proteins (calsequestrin and calreticulin) as determined by Western blotting. Also, the PM Ca2+ pump was present but not connexin 43 (a noncaveolae PM protein), the sarcoplasmic reticulum (SR) Ca2+ pump, or the type 1 inositol 1,4,5-trisphosphate receptor, supporting the idea that SR-derived membranes were not present. Antibodies to caveolin coimmunoprecipitated caveolin with calsequestrin or calreticulin. Thus some of the cellular calsequestrin and calreticulin associated with caveolin on the cytoplasmic face of each caveola. Immunohistochemistry of tracheal smooth muscle crysosections confirmed the localization of caveolin and the PM Ca2+ pump to the cell periphery, whereas the SR Ca2+ pump was located deeper in the cell. The presence of L-type Ca2+ channels, the PM Ca2+ pump, and the Ca2+ bindng proteins calsequestrin and calreticulin in caveolin-enriched membranes supports caveola involvement in airway smooth muscle Ca2+ handling.

Airway smooth muscle excitation-contraction coupling and airway hyperresponsiveness

2005 ◽  
Vol 83 (8-9) ◽  
pp. 725-732 ◽  
Author(s):  
Simon Hirota ◽  
Peter B Helli ◽  
Adriana Catalli ◽  
Allyson Chew ◽  
Luke J Janssen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Signaling Pathways ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Rho Kinase ◽  
Shortness Of Breath ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Hallmark Feature

The primary complaints from patients with asthma pertain to function of airway smooth muscle (ASM) function including shortness of breath, wheezing, and coughing. Thus, it is imperative to better understand the mechanisms underlying excitation-contraction coupling in ASM. Here, we review the various signaling pathways underlying contraction in ASM, and then examine how these are altered in asthma and airway hyperresponsiveness (a hallmark feature of asthma). Throughout, we highlight how studies of vascular smooth muscle have helped or hindered progress in understanding ASM physiology and pathophysiology.Key words: airway smooth muscle, vascular smooth muscle, excitation-contraction coupling, calcium, Rho-kinase.

Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1

2006 ◽  
Vol 291 (6) ◽  
pp. C1326-C1335 ◽  
Author(s):  
Yulia Shakirova ◽  
Johan Bonnevier ◽  
Sebastian Albinsson ◽  
Mikael Adner ◽  
Bengt Rippe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Rho Kinase ◽  
Signaling Proteins ◽  
Muscarinic Agonist ◽  
Smooth Muscle Contractility ◽  
Caveolin 1 ◽  
Femoral Arteries ◽  
Kinase C ◽  
Arterial Contraction ◽  
Relative Mrna Expression

Caveolae are omega-shaped membrane invaginations that are abundant in smooth muscle cells. Since many receptors and signaling proteins co-localize with caveolae, these have been proposed to integrate important signaling pathways. The aim of this study was to test whether RhoA/Rho-kinase and protein kinase C (PKC)-mediated Ca2+ sensitization depends on caveolae using caveolin (Cav)-1-deficient (KO) and wild-type (WT) mice. In WT smooth muscle, caveolae were detected and Cav-1, -2 and -3 proteins were expressed. Relative mRNA expression levels were ∼15:1:1 for Cav-1, -2, and -3, respectively. Caveolae were absent in KO and reduced levels of Cav-2 and Cav-3 proteins were seen. In intact ileum longitudinal muscle, no differences in the responses to 5-HT or the muscarinic agonist carbachol were found, whereas contraction elicited by endothelin-1 was reduced. Rho activation by GTPγS was increased in KO compared with WT as shown using a pull-down assay. Following α-toxin permeabilization, no difference in Ca2+ sensitivity or in Ca2+ sensitization was detected. In KO femoral arteries, phorbol 12,13-dibutyrate (PDBu)-induced and PKC-mediated contraction was increased. This was associated with increased α1-adrenergic contraction. Following inhibition of PKC, α1-adrenergic contraction was normalized. PDBu-induced Ca2+ sensitization was not increased in permeabilized femoral arteries. In conclusion, Rho activation, but not Ca2+ sensitization, depends on caveolae in the ileum. Moreover, PKC driven arterial contraction is increased in the absence of caveolin-1. This depends on an intact plasma membrane and is not associated with altered Ca2+ sensitivity.

Direct effects of hydrogen peroxide on airway smooth muscle tone: Roles of Ca2+ influx and Rho-kinase

2007 ◽  
Vol 556 (1-3) ◽  
pp. 151-156 ◽  
Author(s):  
Katsuyuki Kojima ◽  
Hiroaki Kume ◽  
Satoru Ito ◽  
Tetsuya Oguma ◽  
Akira Shiraki ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Rho Kinase ◽  
Direct Effects ◽  
Smooth Muscle Tone

ENDOTHELIN-1 ACTIVATION IS IMPAIRED IN BLADDER AND CORPORAL SMOOTH MUSCLE OF CAVEOLIN-1-KNOCKOUT MICE

2009 ◽  
Vol 181 (4S) ◽  
pp. 302-302
Author(s):  
Christian Gratzke ◽  
Christian G Stief ◽  
Michael P. Lisanti ◽  
Petter Hedlund ◽  
Karl-Erik Andersson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Knockout Mice ◽  
Caveolin 1 ◽  
Endothelin 1

scholarly journals Mechanisms of BDNF regulation in asthmatic airway smooth muscle

2016 ◽  
Vol 311 (2) ◽  
pp. L270-L279 ◽  
Author(s):  
Bharathi Aravamudan ◽  
Michael A. Thompson ◽  
Christina M. Pabelick ◽  
Y. S. Prakash
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Transient Receptor Potential ◽  
Rho Kinase ◽  
Receptor Potential ◽  
Camp Response Element Binding ◽  
Transient Receptor Potential Channels ◽  
Bdnf Expression ◽  
Activated T Cells ◽  
Tnf Α

Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca2+ regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling.

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