RhoA/Rho-Kinase: Pathophysiologic and Therapeutic Implications in Gastrointestinal Smooth Muscle Tone and Relaxation

Rattan, Satish; Phillips, Benjamin; Maxwell, Pinckney J.

doi:10.1053/j.gastro.2009.11.016

Cited by 53 publications

(56 citation statements)

References 117 publications

(148 reference statements)

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“…While the activated ROCK can phosphorylate the Myosin-Light-Chain Phosphatase (MLCP) to decrease the activity of MLCP, which could suppress the transformation into MLC, resulting in contraction in smooth muscle cells [23]. As long as the RhoA was transferred into non-active state, the activity of ROCK was correspondently decreased, which mediates the relaxation of smooth muscle cells [24]. Our results showed that the mRNA and protein expressions of RhoA and ROCK2 were lower in the Ad-Ang-2 shRNA group than those in the DMED group, but still higher those in the control group.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Silencing Alleviates Erectile Dysfunction Through Down-Regulating the Rhoa/Rho Kinase Signaling Pathway in Rats with Diabetes Mellitus

Zhang

Jia

et al. 2018

Cell Physiol Biochem

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Background/Aims: We aim to explore the role of angiotensin (Ang)II and the RhoA/Rho kinase signaling pathway in the pathogenesis of erectile dysfunction in diabetes mellitus (DM). Methods: Male Sprague-Dawley (SD) rats were used for experiments and short hairpin RNA (shRNA) was used to silence the AngII gene. The erectile function of rats was observed and intracavernous pressure and mean arterial pressure (ICP/MAP) were measured after electrical stimulation. Relaxation and contraction of smooth muscle in the corpus cavernosum were tested. Western blotting and quantitative RT-PCR were applied to measure the expressions of RhoA, Rho-associated kinase (ROCK)1 and ROCK2. Radioimmunoassay was applied to detect the levels of AngII. Results: Rats in the control group had the most erectile times, followed by AngII-silenced rats with DMED and rats with DMED. Rats with DMED had worse ICP and MAP than AngII-silenced rats. The contraction ability was markedly improved and relaxation ability was decreased in AngII-silenced rats with DMED as compared with rats with DMED. The levels of AngII were significantly increased in DMED rats while significantly decreased after AngII silencing. The mRNA and proteins of RhoA and ROCK2 were expressed in a similar way. Conclusion: AngII silencing improves erectile dysfunction via down-regulating the RhoA/Rho kinase signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Silencing Alleviates Erectile Dysfunction Through Down-Regulating the Rhoa/Rho Kinase Signaling Pathway in Rats with Diabetes Mellitus

Zhang

Jia

et al. 2018

Cell Physiol Biochem

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“…Rho-kinase is an enzyme that plays a critical role in various cellular functions, such as changes in cell morphology, cell motility, formation of actin stress fibers and focal adhesions, and cytokine production [5,6]. These functions are integral to contraction, migration, and proliferation of constituent cells, particularly in the gut.…”

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confidence: 99%

Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats

Balyemez

Sivaslı

Ceylan

et al. 2011

Journal of Pediatric Surgery

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“…ROCK-2 plays an important role in the maintenance of sphincter tone in the lower esophagus and internal layer of anal muscle (35). The extent to which ROCK-2 contributes to pyloric sphincter tone has not been previously examined either physiologically or in subjects with IHPS.…”

mentioning

confidence: 99%

Infantile hypertrophic pyloric stenosis (IHPS): A study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease

Welsh

Shifrin

Pan

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Welsh C, Shifrin Y, Pan J, Belik J. Infantile hypertrophic pyloric stenosis (IHPS): A study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease. Am J Physiol Gastrointest Liver Physiol 307: G1198 -G1206, 2014. First published October 30, 2014 doi:10.1152/ajpgi.00221.2014.-Infantile hypertrophic pyloric stenosis (IHPS) is a common disease of unknown etiology. The tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia-1 (hph-1) newborn mouse has a similar phenotype to the human condition. For hph-1 and wild-type control animals, pyloric tissue agonist-induced contractile properties, reactive oxygen species (ROS) generation, cGMP, neuronal nitric oxide synthase (nNOS) content, and Rhoassociated protein kinase 2 (ROCK-2) expression and activity were evaluated. Primary pyloric smooth muscle cells from wild-type newborn animals were utilized to evaluate the effect of BH4 deficiency. One-week-old hph-1 mice exhibited a fourfold increase (P Ͻ 0.01) in the pyloric sphincter muscle contraction magnitude but similar relaxation values when compared with wild-type animals. The pyloric tissue nNOS expression and cGMP content were decreased, whereas the rate of nNOS uncoupling increased (P Ͻ 0.01) in 1-wk-old hph-1 mice when compared with wild-type animals. These changes were associated with increased pyloric tissue ROS generation and elevated ROCK-2 expression/activity (P Ͻ 0.05). At 1-3 days of age and during adulthood, the gastric emptying rate of the hph-1 mice was not altered, and there were no genotype differences in pyloric tissue ROS generation, nNOS expression, or ROCK-2 activity. BH4 inhibition in pyloric smooth muscle cells resulted in increased ROS generation (P Ͻ 0.01) and ROCK-2 activity (P Ͻ 0.05). Oxidative stress upregulated ROCK-2 activity in pyloric tissue, but no changes were observed in newborn fundal tissue in vitro. We conclude that ROSinduced upregulation of ROCK-2 expression accounts for the increased pyloric sphincter tone and nNOS downregulation in the newborn hph-1 mice. The role of ROCK-2 activation in the pathogenesis of IHPS warrants further study. superoxide; Rho-associated protein kinase; smooth muscle SPHINCTER TONE IS DETERMINED by the balance between the neuronal nitric oxide (NO) synthase (nNOS)-dependent relaxant and the Rho-associated protein kinase 2 (ROCK-2)-dependent contraction effects. nNOS is the most abundant NOS isoform in gastrointestinal smooth muscle (42), and its NO generation potential depends on the coupled dimeric state of the enzyme. When uncoupled, nNOS predominantly generates reactive oxygen species (ROS) (11,37,42).Infantile hypertrophic pyloric stenosis (IHPS) is a relatively common disease affecting 2 in 1,000 live births (34) and manifesting clinically at 3-6 wk of age. The IHPS etiology and pathogenesis are unknown, but the increased sphincter tone is believed to be related to reduced pyloric tissue nNOS expression (2) and the resulting lower NO generation (13,34,45). Several experimental animal models of the condition have been studied...

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RhoA/Rho-Kinase: Pathophysiologic and Therapeutic Implications in Gastrointestinal Smooth Muscle Tone and Relaxation

Cited by 53 publications

References 117 publications

Angiotensin II Silencing Alleviates Erectile Dysfunction Through Down-Regulating the Rhoa/Rho Kinase Signaling Pathway in Rats with Diabetes Mellitus

Angiotensin II Silencing Alleviates Erectile Dysfunction Through Down-Regulating the Rhoa/Rho Kinase Signaling Pathway in Rats with Diabetes Mellitus

Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats

Infantile hypertrophic pyloric stenosis (IHPS): A study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease

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