Al-Shboul Othman, Mustafa Ayman
Department of physiology and biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan.
Can J Physiol Pharmacol. 2015 Jun;93(6):405-11. doi: 10.1139/cjpp-2014-0505. Epub 2015 Jan 28.
Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.
最近的研究表明，Rho激酶信号传导和氧化应激均参与多种人类疾病的发病机制，如糖尿病、高血压和动脉粥样硬化。然而，关于氧化应激对胃肠道（GI）平滑肌Rho激酶途径的影响，人们了解甚少。本研究的目的是探讨氧化应激对大鼠胃中Rho激酶II和肌肉收缩的影响。使用过氧亚硝酸盐供体3-吗啉代 sydnonimine（SIN-1）、过氧化氢（H2O2）和过氧亚硝酸盐来诱导氧化应激。分别通过专门设计的酶联免疫吸附测定（ELISA）和活性测定试剂盒，在对照细胞和经氧化剂处理的细胞中测量Rho激酶II的表达和乙酰胆碱（ACh）诱导的活性。在存在或不存在Rho激酶阻滞剂盐酸Y-27632的情况下，通过扫描测微法测量单个平滑肌细胞的收缩。所有氧化剂均显著增加ACh诱导的Rho激酶II活性，而不影响其表达水平。最重要的是，所有三种试剂诱导的氧化应激增强了ACh刺激的肌肉细胞收缩，而Y-27632可显著抑制这种收缩。总之，氧化应激激活Rho激酶II并增强大鼠胃肌的收缩，表明其在与氧化应激相关的胃肠动力障碍中起重要作用。
