Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase

Araki, Shigemasa; M, Ito; Kureishi, Yasuko; Feng, Jianhua; Machida, Hirofumi; Isaka, Naoki; Amano, Mutsuki; Kaibuchi, Kozo; Hartshorne, David J.; Nakano, Takeshi

doi:10.1007/s004240000462

Cited by 77 publications

(54 citation statements)

References 42 publications

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“…Studies show that Rho kinase can be activated by Rho as well as by other second messengers such as arachidonic acid and sphingosylphosphorylcholine (2,34). Therefore, we examined whether Rho is involved in activation of Rho kinase in ROS-treated aortic rings.…”

Section: Discussionmentioning

confidence: 99%

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Jin

Zhao

Webb

2004

American Journal of Physiology-Heart and Circulatory Physiology

224

185

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. Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. Am J Physiol Heart Circ Physiol 287: H1495-H1500; 2004; 10.1152/ajpheart.01006.2003.-Evidence indicates that both the Rho/ Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H 2O2 are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 M) significantly reduced X/XOinduced contraction. A Rho kinase inhibitor, (ϩ)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca 2ϩ -independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca 2ϩ sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca 2ϩ -independent PKC. myosin light chain phosphatase; smooth muscle contraction; antioxidants CONTRACTION OF SMOOTH MUSCLE is regulated by both Ca 2ϩ -dependent and Ca 2ϩ -independent (Ca 2ϩ sensitization) mechanisms. A rise in intracellular Ca 2ϩ levels leads to myosin light chain (MLC) kinase activation, resulting in an increase in MLC phosphorylation. Importantly, MLC phosphorylation can also be increased through inhibition of MLC phosphatase, which augments smooth muscle force generation without a change in intracellular Ca 2ϩ (38).In recent years, studies have revealed that the small GTPase Rho and its downstream target Rho kinase mediate the Ca 2ϩ sensitization of smooth muscle contraction (37). The exchange of bound GDP for GTP activates Rho and stimulates its translocation from cytosol to membrane. Rho-GTP phosphorylates Rho kinase, which inhibits MLC phosphatase activity by phosphorylation of the MLC phosphatase target subunit (MYPT1). A decrease in MLC phosphatase activity increases phosphorylation of myosin and therefore contributes to smooth muscle contraction at low levels of intracellular Ca 2ϩ concentration. Strong evidence suggests that increased Rho/Rho kinase-dependent Ca 2ϩ sensitization contributes to hypertension and inhibition of Rho or Rho kinase reduces blood pressure (33, 42). Some heterotrimetric G protein-coupled receptor (GPCR) agonists, including angiotensin II (ANG II) and endothelin (ET)-1, induce smooth mus...

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Section: Discussionmentioning

confidence: 99%

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Jin

Zhao

Webb

2004

American Journal of Physiology-Heart and Circulatory Physiology

224

185

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“…Ca 2 þ sensitizing mechanisms mediated through arachidonic acid and MAP kinase (Cain et al, 2002) have been reported. Recently, it was reported that arachidonic acid-induced Ca 2 þ sensitization in a-toxin-permeabilized rabbit femoral artery was inhibited by Y-27632 (Araki et al, 2001), suggesting that arachidonic acid activates the rho pathway. MAP kinase was shown to be activated by acetylcholine in canine colonic smooth muscles (Gerthoffer et al, 1996).…”

Section: T Takeuchi Et Almentioning

confidence: 99%

Mechanisms involved in carbachol‐induced Ca²⁺ sensitization of contractile elements in rat proximal and distal colon

Takeuchi

Kushida

Hirayama

et al. 2004

British J Pharmacology

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1 Mechanisms involved in Ca 2 þ sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied. 2 In a-toxin-permeabilized preparations from the rat proximal and distal colon, Ca 2 þ induced a rapid phasic and subsequent tonic component. After Ca 2 þ -induced contraction reached a plateau, guanosine 5 0 -triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparations of both the proximal and distal colon (Ca 2 þ sensitization). 3 Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced Ca 2 þ sensitization more significantly in the proximal colon than in the distal colon. Y-27632 at 10 mM had no effect on Ca 2 þ -induced contraction or slightly inhibited phorbol-12,13-dibutyrate-induced Ca 2 þ sensitization in either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor, inhibited GTP plus CChinduced Ca 2 þ sensitization in the distal colon, but not in the proximal colon. The component of Ca 2 þ sensitization that persisted after the chelerythrine treatment was completely inhibited by Y-27632. 4 In b-escin-permeabilized preparations of the proximal colon, C3 exoenzyme completely inhibited GTP plus CCh-induced Ca 2 þ sensitization, but PKC(19-31) did not. In the distal colon, C3 exoenzyme abolished GTP-induced Ca 2 þ sensitization. It inhibited CCh-induced sensitization by 50 % and the remaining component was inhibited by PKC(19-31). 5 These results suggest that both protein kinase C and rho pathways in parallel mediate the Ca 2 þ sensitization coupled to activation of muscarinic receptors in the rat distal colon, whereas the rho pathway alone mediates this action in the proximal colon.

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“…Several downstream signaling pathways that inhibit myosin phosphatase activity have been discovered recently, including RhoA/Rho kinase (21), protein kinase C activation of the inhibitory phosphoprotein CPI-17 (22), and arachidonic acid (23,24). In addition, several kinases copurify with myosin phosphatase, including ZIP-like kinase (25), integrin-linked kinase (26), myotonic dystrophy-related kinase (27), and Raf-1 (28), each of which can phosphorylate MBS and inhibit myosin phosphatase activity.…”

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confidence: 99%

Myosin Phosphatase-Rho Interacting Protein

Surks

Richards

Mendelsohn

2003

Journal of Biological Chemistry

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Regulation of vascular smooth muscle cell contractile state is critical for the maintenance of blood vessel tone. Abnormal vascular smooth muscle cell contractility plays an important role in the pathogenesis of hypertension, blood vessel spasm, and atherosclerosis. Myosin phosphatase, the key enzyme controlling myosin light chain dephosphorylation, regulates smooth muscle cell contraction. Vasoconstrictor and vasodilator pathways inhibit and activate myosin phosphatase, respectively. G-protein-coupled receptor agonists can inhibit myosin phosphatase and cause smooth muscle cell contraction by activating RhoA/Rho kinase, whereas NO/cGMP can activate myosin phosphatase and cause smooth muscle cell relaxation by activation of cGMP-dependent protein kinase. We have used yeast two-hybrid screening to identify a 116-kDa human protein that interacts with both myosin phosphatase and RhoA. This myosin phosphatase-RhoA interacting protein, or M-RIP, is highly homologous to murine p116 RIP3 , is expressed in vascular smooth muscle, and is localized to actin myofilaments. Blood vessel tone is regulated by the contractile state of vascular smooth muscle cells in the blood vessel wall. Diseases characterized by abnormal vascular smooth muscle cell contraction include hypertension, blood vessel spasm, and atherosclerosis (1-5). Smooth muscle contraction is tightly coupled to myosin light chain phosphorylation (6), which in turn is regulated by the relative activities of myosin light chain kinase and myosin phosphatase. Myosin light chain kinase is activated by intracellular calcium and phosphorylates myosin light chains, leading to cell contraction (7,8). Myosin phosphatase dephosphorylates myosin light chains, leading to smooth muscle cell relaxation (9). Myosin phosphatase activity, once thought to be constitutive, is now known to be highly regulated. Both vasoconstrictor signaling pathways, which lead to inhibition of the phosphatase and cell contraction (reviewed in Ref. 10), and vasodilator signaling pathways, which lead to cell relaxation via activation of myosin phosphatase have been recently defined (11-15).Myosin phosphatase is a heterotrimer consisting of a PP1 catalytic subunit, a 130-kDa myosin binding subunit (MBS) 1 and a 20-kDa subunit of unknown function (9, 16 -18). The MBS is a regulatory subunit that targets PP1 to its substrate, myosin light chain (9), and has multiple protein interaction domains, including ankyrin repeats at its amino terminus, and a leucine zipper domain at its carboxyl terminus. MBS binds PP1 and myosin light chain at its amino terminus and the M20 subunit and cGMP-dependent protein kinase 1␣ (cGK) at its carboxyl terminus (Ref. 11, reviewed in Ref. 19). The MBS-cGK interaction is necessary for NO/cGMP-mediated activation of myosin phosphatase (11).In vascular smooth muscle, G-protein-coupled receptor agonists cause contraction in part by inhibition of myosin phosphatase activity (20). Several downstream signaling pathways that inhibit myosin phosphatase activity have been discovered re...

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Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase

Cited by 77 publications

References 42 publications

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Mechanisms involved in carbachol‐induced Ca²⁺ sensitization of contractile elements in rat proximal and distal colon

Myosin Phosphatase-Rho Interacting Protein

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Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase

Cited by 77 publications

References 42 publications

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Mechanisms involved in carbachol‐induced Ca2+ sensitization of contractile elements in rat proximal and distal colon

Myosin Phosphatase-Rho Interacting Protein

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Mechanisms involved in carbachol‐induced Ca²⁺ sensitization of contractile elements in rat proximal and distal colon