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rho kinase

Haitao Luo, Caixia Liang
Non-small cell lung cancer (NSCLC) accounts for ~80% of all types of lung cancer, which has the highest morbidity and mortality of all types of cancer worldwide. It is important to identify novel biomarkers and the molecular mechanism of NSCLC to improve current treatments of NSCLC. The present study aimed to investigate the effect of miR-148b expression on the proliferation, epithelial-mesenchymal transition (EMT) and radiosensitivity of NSCLC cells. It was demonstrated that miR-148b expression was significantly decreased in NSCLC tissues and cell lines...
April 2018: Experimental and Therapeutic Medicine
Danuta Jarocha, Karen K Vo, Randolph B Lyde, Vincent Hayes, Rodney M Camire, Mortimer Poncz
In vitro-grown megakaryocytes for generating platelets may have value in meeting the increasing demand for platelet transfusions. Remaining challenges have included the poor yield and quality of in vitro-generated platelets. We have shown that infusing megakaryocytes leads to intrapulmonary release of functional platelets. A Src kinase inhibitor (SU6656), a Rho-associated kinase inhibitor (Y27632), and an aurora B kinase inhibitor (AZD1152) have been shown to increase megakaryocyte ploidy and in vitro proplatelet release...
March 27, 2018: Blood Advances
Hao Wang, Mingxia Zhang, Guoping Sun
This study aimed to elucidate the roles of long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) in gastric cancer. The expression of NEAT1 in gastric cancer tissues and cells was determined. NEAT1 was then overexpressed and suppressed in BGC-823 cells in vitro to further explore the effects of NEAT1 on cell proliferation, migration, and invasion. In addition, the regulatory relationship among NEAT1, miR-335-5p and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was investigated...
March 5, 2018: Die Pharmazie
Verónica M Negrón-Pérez, Luana Teixeira Rodrigues, Gisele Zoccal Mingoti, Peter J Hansen
Rho-associated coiled-coil containing protein kinases (ROCK1 and ROCK2) are activated by binding to RHO GTPases and phosphorylate a variety of downstream targets including actinomyosin. In the mouse embryo, ROCK signaling acts to promote formation of trophectoderm (TE) and inhibit formation of the inner cell mass (ICM) by polarizing outer cells of the embryo to inactivate Hippo signaling (Kono et al., 2014; Mihajlović and Bruce, 2016). This article is protected by copyright. All rights reserved.
March 15, 2018: Molecular Reproduction and Development
Heather L Lehman, Michal Kidacki, Joshua I Warrick, Douglas B Stairs
Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of poor prognosis in ESCC. In a previous study we demonstrated that in our 3D organotypic culture model, only when EGFR overexpression is combined with p120ctn inactivation do the cells transform and invade - as opposed to either event alone...
February 16, 2018: Oncotarget
Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, John Bush, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro
BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs...
March 15, 2018: New England Journal of Medicine
Jerry C Madukwe, Elisabeth E Garland-Kuntz, Angeline M Lyon, Alan V Smrcka
Phospholipase C (PLC) enzymes hydrolyze membrane phosphatidylinositol 4,5 bisphosphate (PIP2) and regulate Ca2+ and protein kinase signaling in virtually all mammalian cell types. Chronic activation of the PLCɛ isoform downstream of G protein-coupled receptors (GPCRs) contributes to the development of cardiac hypertrophy. We have previously shown that PLCε-catalyzed hydrolysis of Golgi-associated phosphatidylinositol 4-phosphate (PI4P) in cardiac myocytes depends on G protein βγ subunits released upon stimulation with endothelin-1...
March 13, 2018: Journal of Biological Chemistry
T Michael De Silva, Mary L Modrick, Fabrice Dabertrand, Frank M Faraci
Vascular aging fundamentally contributes to large and small vessel disease. Despite the importance of such changes for brain function, mechanisms that mediate such changes are poorly defined. We explored mechanisms that underlie changes with age, testing the hypothesis that ROCK (Rho kinase) plays an important role. In C57BL/6 mice, baseline diameters of isolated pressurized parenchymal arterioles were similar in adult (4-5 month) and old mice (22±1 month; ≈15±1 µm). Endothelium-dependent dilation was impaired in old mice compared with adults in a pathway-specific manner...
March 12, 2018: Hypertension
Iris Lim, Russ Chess-Williams, Donna Sellers
This study investigated the role of calcium sensitisation in the regulation of ureteral contractility with ageing. Isolated ureteral strips from young (6-month old) and older (3-year old) pigs were mounted in Krebs bicarbonate solution and contractility induced by the α1-adrenoceptor agonist phenylephrine (30 and 300 μM) and 5-HT (10 and 100 μM), recorded in the absence and presence of the rho-kinase inhibitors Y-27632 (10 μM) and fasudil (30 μM). Ureteral strips developed bursts of contractile activity which was measured as area under the curve (AUC) and frequency...
March 9, 2018: Mechanisms of Ageing and Development
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
Yuan Dai, Weijia Luo, Jiang Chang
Rho kinases (ROCKs) are the first discovered RhoA effectors that are now widely known for their effects on actin organization. Recent studies have shown that ROCKs play important roles in cardiac physiology. Abnormal activation of ROCKs participate in multiple cardiovascular pathological processes, including cardiac hypertrophy, apoptosis, fibrosis, systemic hypertension, and pulmonary hypertension. ROCK inhibitors, fasudil and statins, have shown beneficial cardiovascular effects in many animal studies, clinical trials, and applications...
February 2018: Current Opinion in Physiology
Etsuo Chihara, Galina Dimitrova, Tomoyuki Chihara
PURPOSE: To assess the responses of the superficial peripapillary retinal vessel density (VD) and prelaminar flow index (PLFI) to topical Rho-assisted coiled-coil forming protein kinase (ROCK) inhibitor ripasudil and alpha-2 agonist brimonidine using optical coherence tomography angiography. METHODS: This is a prospective, non-randomized, comparative cohort study. We studied the response of optical coherence tomography angiography (OCTA) parameters to drugs in 24 eyes treated with ripasudil and 23 eyes treated with brimonidine at the Sensho-kai Eye Institute...
March 8, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
Jinlan He, Lei Cai, Ye Chen, Yan He, Ming Wang, Jie Tang, Hui Guan, Jingjing Wang, Xingchen Peng
BACKGROUND AND PURPOSE: SKLB-163 is a novel benzothiazole-2-thiol derivative with antitumor activities. This study investigated the effects of SKLB-163 on nasopharyngeal carcinoma (NPC) and its mechanisms. MATERIALS AND METHODS: Rho GDP-dissociation inhibitor (RhoGDI) expression was examined in NPC cell lines by western blot. Effects of SKLB-163 on proliferation, migration and radiosensitivity were assessed by MTT, wound healing and colony formation assays in vitro...
March 5, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Hironori Inaba, Daishi Yamakawa, Yasuko Tomono, Atsushi Enomoto, Shinji Mii, Kousuke Kasahara, Hidemasa Goto, Masaki Inagaki
We previously reported that vimentin, GFAP, and desmin (type III intermediate filament [IF] proteins) are mitotically phosphorylated by CDK1, Aurora-B, and Rho-kinase. This phosphorylation is critical for efficient separation of these IFs and completion of cytokinesis. Keratin 5 (K5) and K14 form a heterodimer, which constitutes IF network in basal layer cells of stratified squamous epithelia. Here, we report that the solubility of K5/K14 increased in mitosis. The in vitro assays revealed that three mitotic kinases phosphorylate K5 more than K14...
March 5, 2018: Biochemical and Biophysical Research Communications
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
Juhyun Park, Sung Yong Cho, Kwanjin Park, Ji Sun Chai, Hwancheol Son, Soo Woong Kim, Jae-Seung Paick, Min Chul Cho
We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2...
March 6, 2018: Asian Journal of Andrology
Mingshuai Wang, Nianzeng Xing, Liyang Wu, Wen-Chu Huang, Zhenqun Xu, Guiming Liu
Enhanced spontaneous contractions are associated with overactive bladder. Elevated levels of reactive oxygen species might contribute to enhanced spontaneous contractions. We investigated the regulation of spontaneous contractions and the effects of hydrogen peroxide (H2 O2 ) in intact rat bladder strips. The spontaneous contractions were measured using a tissue bath system. The vehicle or the specific activators/blockers were applied and followed by the application of 0.003 g% H2 O2 . The basal tension, amplitude, and frequency of spontaneous contractions were quantified...
2018: BioMed Research International
Virginia Tajadura-Ortega, Ritu Garg, Richard Allen, Claudia Owczarek, Michael D Bright, Samuel Kean, Aisyah Mohd-Noor, Anita Grigoriadis, Timothy C Elston, Klaus M Hahn, Anne J Ridley
BACKGROUND: Cell migration is essential for development and tissue repair, but it also contributes to disease. Rho GTPases regulate cell migration, but a comprehensive analysis of how each Rho signalling component affects migration has not been carried out. RESULTS: Through an RNA interference screen, and using a prostate cancer cell line, we find that approximately 25% of Rho network components alter migration. Some genes enhance migration while others decrease basal and/or hepatocyte growth factor-stimulated migration...
March 6, 2018: BMC Biology
Xiaowen Zhang, Nan Wu
Background: Rho-kinase signal pathway is a new target for cancer therapy. Fasudil, a selective Rho-kinase inhibitor, is found to exert antitumor effects on several types of cancer, but whether fasudil has antitumor effects on laryngeal carcinoma is still unknown. The aim of this study was to determine the effects of fasudil on laryngeal carcinoma and explore the underlying molecular mechanisms in this process. Methods: After treatment with fasudil, changes in biological behaviors, including the growth, proliferation, clone formation, apoptosis, and migration of human laryngeal carcinoma cells (Hep-2 cells) were observed...
2018: Drug Design, Development and Therapy
Victor S C Wong, Cristina Picci, Michelle Swift, Max Levinson, Dianna Willis, Brett Langley
Damage to the CNS results in neuronal and axonal degeneration, and subsequent neurological dysfunction. Endogenous repair in the CNS is impeded by inhibitory chemical and physical barriers, such as chondroitin sulfate proteoglycans (CSPGs) and myelin-associated glycoprotein (MAG), which prevent axon regeneration. Previously, it has been demonstrated that the inhibition of axonal histone deacetylase-6 (HDAC6) can promote microtubule α-tubulin acetylation and restore the growth of CSPGs- and MAG-inhibited axons...
January 2018: ENeuro
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