Decreased myosin phosphatase target subunit 1(MYPT1) phosphorylation via attenuated rho kinase and zipper-interacting kinase activities in edematous intestinal smooth muscle.
Decreased myosin phosphatase target subunit 1(MYPT1) phosphorylation via attenuated rho kinase and zipper-interacting kinase activities in edematous intestinal smooth muscle.
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DOI：
10.1111/j.1365-2982.2011.01855.x
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发表时间：
2012-03
影响因子：
3.5
通讯作者：
Uray KS
中科院分区：
文献类型：
--
作者：
Chu J;Miller CT;Kislitsyna K;Laine GA;Stewart RH;Cox CS;Uray KS
创伤复苏后肠水肿的发展抑制肠动力，导致肠梗阻，阻止肠内喂养和损害患者的预后。我们以前已经表明，减少肠蠕动与减少平滑肌肌球蛋白轻链（MLC）磷酸化。本研究的目的是探讨在啮齿动物肠水肿模型中，水肿诱导MLC减少的机制。肠水肿是由复苏液管理和肠系膜静脉高压的组合。假手术动物作为对照。测量收缩活动和MLC调节的改变，包括MLC激酶（MLCK）和MLC磷酸酶（MLCP）的调节。与非水肿组织相比，水肿肠平滑肌的收缩幅度和基础张力显著降低。与非水肿肠平滑肌相比，水肿组织中的钙敏感性也降低。虽然与非水肿组织相比，MLCK的抑制在水肿组织中显著降低收缩活性，但组织裂解物中的MLCK活性没有显著差异。与非水肿组织相比，水肿组织中MYPT的磷酸化显著较低。此外，rho激酶和拉链相互作用激酶的活性在水肿组织中显著降低。我们从这些数据中得出结论，间质性肠水肿主要通过降低ROCK和ZIPK活性降低MLC磷酸酶的MLC靶向亚基（MYPT 1）的抑制性磷酸化来抑制MLC磷酸化，从而导致更多的MLC磷酸酶活性。
Intestinal edema development after trauma resuscitation inhibits intestinal motility which results in ileus, preventing enteral feeding and compromising patient outcome. We have shown previously that decreased intestinal motility is associated with decreased smooth muscle myosin light chain (MLC) phosphorylation. The purpose of the present study was to investigate the mechanism of edema-induced decreases in MLC in a rodent model of intestinal edema. Intestinal edema was induced by a combination of resuscitation fluid administration and mesenteric venous hypertension. Sham operated animals served as controls. Contractile activity and alterations in the regulation of MLC including the regulation of MLC kinase (MLCK) and MLC phosphatase (MLCP) were measured. Contraction amplitude and basal tone were significantly decreased in edematous intestinal smooth muscle compared to non-edematous tissue. Calcium sensitivity was also decreased in edematous tissue compared to non-edematous intestinal smooth muscle. Although inhibition of MLCK decreased contractile activity significantly less in edematous tissue compared to non-edematous tissue, MLCK activity in tissue lysates was not significantly different. Phosphorylation of MYPT was significantly lower in edematous tissue compared to non-edematous tissue. In addition, activities of both rho kinase and zipper-interacting kinase were significantly lower in edematous tissue. We conclude from these data that interstitial intestinal edema inhibits MLC phosphorylation predominantly by decreasing inhibitory phosphorylation of the MLC targeting subunit (MYPT1) of MLC phosphatase via decreased ROCK and ZIPK activities, resulting in more MLC phosphatase activity.
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影响因子：
4.8
作者：
Kureishi, Y;Kobayashi, S;Ito, M
通讯作者：
Ito, M
影响因子：
3.1
作者：
Cox, Charles S., Jr.;Radhakrishnan, Ravi;Laine, Glen A.
通讯作者：
Laine, Glen A.
影响因子：
8.8
作者：
Radhakrishnan, Ravi S.;Radhakrishnan, Hari R.;Cox, Charles S., Jr.
通讯作者：
Cox, Charles S., Jr.
影响因子：
4.8
作者：
Deng, JT;Van Lierop, JE;Walsh, MP
通讯作者：
Walsh, MP
影响因子：
2.2
作者：
Moore-Olufemi, SD;Xue, H;Cox, CS
通讯作者：
Cox, CS