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Role of RhoA/Rho-kinase and Calcium Sensitivity in Airway Smooth Muscle Functions

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Calcium Signaling In Airway Smooth Muscle Cells

Abstract

Changes in the contractility of airway smooth muscle (ASM) play important roles in bronchoconstriction and airway hyperresponsiveness associated with the pathophysiology of asthma and possibly, in part, chronic obstructive pulmonary disease (COPD). A common feature associated with ASM contraction is phosphorylation of myosin light chain (MLC), which is determined by the balance between MLC kinase (MLCK) and MLC phosphatase (MLCP) activities. MLCK is activated by increases in the intracellular Ca2+ concentration ([Ca2+]i), whereas MLCP is inactivated by Rho-kinase, a target protein of RhoA, independently of [Ca2+]i. The latter mechanism, contraction due to MLCP inhibition mediated by RhoA/Rho-kinase, is a major type of Ca2+ sensitization. Phosphorylation of the 17-kD myosin phosphatase inhibitor protein by protein kinase C is another mechanism of Ca2+ sensitization via MLCP suppression. This chapter focuses on recent evidence regarding regulation of ASM contraction by the RhoA/Rho-kinase pathway and the possible roles of this pathway in the pathogenesis of asthma and COPD.

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Abbreviations

ASM:

airway smooth muscle

[Ca2+]i :

intracellular Ca2+ concentration

COPD:

chronic obstructive pulmonary disease

CPI-17:

17-kD myosin phosphatase inhibitor protein

GAP:

GTPase-activating protein

GDI:

guanine nucleotide dissociation inhibitor

GDP:

guanosine diphosphate

GEF:

guanine nucleotide exchange factor

G protein:

GTP-binding protein

GTP:

guanosine trisphosphate

IL:

interleukin

IP3 :

inositol 1,4,5-trisphosphate

MBS:

myosin-binding subunit

MLC:

myosin light chain

MLCK:

myosin light chain kinase

MLCP:

myosin light chain phosphatase

PDGF:

platelet-derived growth factor

PKA:

protein kinase A

PKC:

protein kinase C

Ser:

serine

S1P:

sphingosine 1-phosphate

SR:

sarcoplasmic reticulum

Thr:

threonine

TNF-α:

tumor necrosis factor-α

TRP:

transient receptor potential

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Acknowledgments

This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (17790531, 19689017, and 22590837). We also thank Ms. Katherine Ono for providing language help.

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  1. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Satoru Ito M.D., Ph.D.

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Correspondence to Satoru Ito M.D., Ph.D. .

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  1. Albany Medical College Center for Cardiovascular Sciences, Albany, New York, USA

    Yong-Xiao Wang

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Ito, S. (2014). Role of RhoA/Rho-kinase and Calcium Sensitivity in Airway Smooth Muscle Functions. In: Wang, YX. (eds) Calcium Signaling In Airway Smooth Muscle Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-01312-1_15

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