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rho kinase

Kangwook Lee, Sung-Gook Cho, Sang-Mi Woo, Ah Jeong Kim, Kang Min Lee, Ho Yeon Go, Seung-Ho Sun, Tae-Hun Kim, Ki-Yong Jung, You-Kyung Choi, Eun Mee Lim, Yun-Kyung Song, Jong-Hyeong Park, Chan-Yong Jun, Seong-Gyu Ko
Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25˚C)‑induced RhoA activation and endothelin‑1 (ET‑1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated...
October 5, 2016: Molecular Medicine Reports
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Lijun Du, John J Kim, Jinhua Shen, Ning Dai
The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn's disease (CD), ulcerative colitis (UC), celiac disease, and irritable bowel syndrome (IBS). Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK-) and myosin light chain kinase- (MLCK-) mediated pathways are involved in the regulation of intestinal permeability...
2016: Gastroenterology Research and Practice
Sung-Hee Hwang, Byung-Hwan Lee, Sun-Hye Choi, Hyeon-Joong Kim, Kyung Jong Won, Hwan Myung Lee, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng...
October 2016: Journal of Ginseng Research
Delyan R Mutavchiev, Marcin Leda, Kenneth E Sawin
The Rho family GTPase Cdc42 is a key regulator of eukaryotic cellular organization and cell polarity [1]. In the fission yeast Schizosaccharomyces pombe, active Cdc42 and associated effectors and regulators (the "Cdc42 polarity module") coordinate polarized growth at cell tips by controlling the actin cytoskeleton and exocytosis [2-4]. Localization of the Cdc42 polarity module to cell tips is thus critical for its function. Here we show that the fission yeast stress-activated protein kinase Sty1, a homolog of mammalian p38 MAP kinase, regulates localization of the Cdc42 polarity module...
October 1, 2016: Current Biology: CB
Benoît Peyronnet, Thomas Seisen, Véronique Phé, Vincent Misrai, Alexandre de la Taille, Morgan Rouprêt
AIM: To provide a systematic review of epidemiological data regarding the association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men. SEARCH STRATEGY: A research has been conducted on the Medline database using the keywords: ("erectile dysfunction" or "sexual dysfunction") and ("benign prostatic hyperplasia" or "lower urinary tract symptoms"). The eligibility of studies was defined using the PICOS method in accordance with the PRISMA statement...
October 10, 2016: La Presse Médicale
Priscila de Souza, Karla Lorena Guarido, Karin Scheschowitsch, Luísa Mota da Silva, Maria Fernanda Werner, Jamil Assreuy, José Eduardo da Silva-Santos
We investigated long-lasting changes in endothelial and vascular function in adult rat survivors of severe sepsis induced by cecal ligation and puncture (CLP) model. For this, male Wistar rats (200-350g) had their cecum punctured once (non-transfixing hole) with a 14-gauge needle. Performed in this way, a mortality rate around 30% was achieved in the first 72h. The survivors, together with age-matched control rats (not subjected to CLP), were maintained in our holding room for 60 days (S60 group) and had the descending thoracic aorta processed for functional, histological, biochemical or molecular analyses...
September 30, 2016: Redox Biology
Keiji Ohata, Toyofumi F Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date
BACKGROUND: Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI. METHODS: The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each)...
October 12, 2016: Annals of Thoracic Surgery
Shaofeng Yan, Hao Xue, Ping Zhang, Xiao Han, Xing Guo, Guang Yuan, Lin Deng, Gang Li
Matrix metalloproteinases (MMPs) play the important role in the process of glioblastoma cell invasion through 3D matrices. However, the effects of MMP inhibitors used in the treatment of malignant gliomas are unsatisfactory. The aim of this study was to explore the reason and mechanism by which cells move through the dense extracellular matrix without proteolysis. The results showed that MMP inhibitor (MMPI), Ilomastat, induced glioma cells to have an amoeboid-like morphology with invasive ability. Moreover, the RhoA/Rho kinase (ROCK)/myosin light chain (MLC) signal is involved in the MMPI-induced movement mode switch, and RhoA activation is dependent on P115RhoGEF...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Nelly Redolfi, Luisa Galla, Andrea Maset, Luca Murru, Eleonora Savoia, Ilaria Zamparo, Angela Gritti, Pierre Billuart, Maria Passafaro, Claudia Lodovichi
Among the X-linked genes associated to intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well established mouse model of X-linked intellectual disability, i...
October 13, 2016: Human Molecular Genetics
Christina Stoeckle, Barbara Geering, Shida Yousefi, Saša Rožman, Nicola Andina, Charaf Benarafa, Hans-Uwe Simon
Eosinophils are frequently elevated in pathological conditions and can cause tissue damage and disease exacerbation. The number of eosinophils in the blood is largely regulated by factors controlling their production in the bone marrow. While several exogenous factors, such as interleukin-5, have been described to promote eosinophil differentiation, comparatively little is known about eosinophil-intrinsic factors that control their de novo generation. Here, we report that the small atypical GTPase RhoH is induced during human eosinophil differentiation, highly expressed in mature blood eosinophils and further upregulated in patients suffering from a hypereosinophilic syndrome...
October 14, 2016: Cell Death and Differentiation
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Lauren P Shapiro, Ryan G Parsons, Anthony J Koleske, Shannon L Gourley
The prevalence of depression, anxiety, schizophrenia, and drug and alcohol use disorders peaks during adolescence. Further, up to 50% of "adult" mental health disorders emerge in adolescence. During adolescence, the prefrontal cortex (PFC) undergoes dramatic structural reorganization, in which dendritic spines and synapses are refined, pruned, and stabilized. Understanding the molecular mechanisms that underlie these processes should help to identify factors that influence the development of psychiatric illness...
October 13, 2016: Journal of Neuroscience Research
Simon Lin, Frank V Brozovich
Agonist stimulation of smooth muscle is known to activate RhoA/Rho kinase signaling, and Rho kinase phosphorylates the myosin targeting subunit (MYPT1) of myosin light chain (MLC) phosphatase at Thr696 and Thr853, which inhibits the activity of MLC phosphatase to produce a Ca(2+) independent increase in MLC phosphorylation and force (Ca(2+) sensitization). Alternative mRNA splicing produces four MYPT1 isoforms, which differ by the presence or absence of a central insert (CI) and leucine zipper (LZ). This study was designed to determine if Rho kinase differentially phosphorylates MYPT1 isoforms...
2016: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
Zhijun Sun, Xing Wu, Weiping Li, Hui Peng, Xuhua Shen, Lu Ma, Huirong Liu, Hongwei Li
BACKGROUND: Diabetes-induced vascular dysfunction may arise from reduced nitric oxide (NO) availability, following interaction with superoxide to form peroxynitrite. Peroxynitrite can induce formation of 3-nitrotyrosine-modified proteins. RhoA/ROCK signaling is also involved in diabetes-induced vascular dysfunction. The study aimed to investigate possible links between Rho/ROCK signaling, hyperglycemia, and peroxynitrite in small coronary arteries. METHODS: Rat small coronary arteries were exposed to normal (NG; 5...
October 11, 2016: BMC Cardiovascular Disorders
Haojie Wang, Yi Wang, Bing Liang, Fei He, Yong Li, Jianbo Che, Xiaohui Li, Hui Zhao, Gongning Shi
OBJECTIVES: The objective of this study was to investigate the expression pattern, functions, and possible mechanisms of RhoE/Rnd3, a novel member of the Rho GTPases family, in human esophageal squamous cell carcinoma (ESCC) cells by using molecular and cell-based experiments. MATERIALS AND METHODS: Quantitative polymerase chain reaction and Western blotting were carried out to determine the mRNA and protein expression of RhoE in ESCC cell lines, respectively. Both 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide (MTT) and flow cytometry were applied to evaluate the effects of RhoE overexpression on ESCC cell growth and apoptosis...
October 2016: Journal of Cancer Research and Therapeutics
Susanne Mühlich, Margot Rehm, Astrid Ebenau, Margarete Goppelt-Struebe
Changes in cell morphology that involve alterations of the actin cytoskeleton are a hallmark of diseased renal tubular epithelial cells. While the impact of actin remodeling on gene expression has been analyzed in many model systems based on cell lines, this study investigated human primary tubular epithelial cells isolated from healthy parts of tumor nephrectomies. Latrunculin B (LatB) and cytochalasin D (CytoD) were used to modulate G-actin levels in a receptor-independent manner. Both compounds (at 0.5μM) profoundly altered F-actin structures in a Rho kinase-dependent manner, but only CytoD strongly induced the pro-fibrotic factor CTGF (connective tissue growth factor)...
October 6, 2016: Cellular Signalling
William R Holmes, Adriana E Golding, William M Bement, Leah Edelstein-Keshet
Rho GTPases are regulatory proteins whose patterns on the surface of a cell affect cell polarization, cell motility and repair of single-cell wounds. The stereotypical patterns formed by two such proteins, Rho and Cdc42, around laser-injured frog oocytes permit experimental analysis of GTPase activation, inactivation, segregation and crosstalk. Here, we review the development and analysis of a spatial model of GTPase dynamics that describe the formation of concentric zones of Rho and Cdc42 activity around wounds, and describe how this model has provided insights into the roles of the GTPase effector molecules protein kinase C (PKCβ and PKCη) and guanosine nucleotide dissociation inhibitor (GDI) in the wound response...
October 6, 2016: Interface Focus
Seong-Ho Ok, Seong-Chun Kwon, Jiseok Baik, Jeong-Min Hong, Jiah Oh, Jeong Yeol Han, Ju-Tae Sohn
Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The effect of Y-27632 and chelerythrine on the dexmedetomidine-induced intracellular calcium concentration ([Ca(2+)]i) and tension were assessed using fura-2-loaded aortic strips...
September 30, 2016: International Journal of Molecular Sciences
Mengsi Hu, Minghua Fan, Junhui Zhen, Jiangong Lin, Qun Wang, Zhimei Lv, Rong Wang
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet-induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder-related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found...
October 5, 2016: Journal of Cellular and Molecular Medicine
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