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https://www.readbyqxmd.com/read/27921230/upregulation-of-rock2-in-gastric-cancer-cell-promotes-tumor-cell-proliferation-metastasis-and-invasion
#1
Manhua Li, Jing Ke, Qiuhong Wang, Hongyan Qian, Lei Yang, Xunlei Zhang, Jinzhang Xiao, Haifang Ding, Xiaohang Shan, Qingqing Liu, Ying Xiao, Bojun Bao, Hua Huang
Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) has been known as an effector for the small GTPase Rho and plays an important role in tumor progression and metastasis. However, the effect of ROCK2 in gastric cancer (GC) has not been identified. This study showed that ROCK2 expression significantly increased in clinical GC tissues compared with adjacent non-cancer tissues. Immunohistochemistrical analysis showed that high expression of ROCK2 was correlated with tumor grade, tumor-node-metastasis stage, infiltration depth, lymph node invasion and Ki-67, and predicted poor prognosis in 135 gastric cancer specimens...
December 5, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27921081/a-fungus-specific-protein-domain-is-essential-for-rasa-mediated-morphogenetic-signaling-in-aspergillus-fumigatus
#2
Qusai Al Abdallah, Tiffany S Norton, Amy M Hill, Lawrence L LeClaire, Jarrod R Fortwendel
Ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. Here, we report the identification of a novel N-terminal domain of the RasA protein in the filamentous fungus Aspergillus fumigatus. Whereas this domain is absent in Ras homologs of higher eukaryotes, the N-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating in an invariant arginine...
November 2016: MSphere
https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#3
Hiroyuki Takeda, Masashi Okada, Shuhei Suzuki, Kenta Kuramoto, Hirotsugu Sakaki, Hikaru Watarai, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka
BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918830/the-antiangiogenic-effects-of-gold-nanoparticles-on-experimental-choroidal-neovascularization-in-mice
#4
Young-Jung Roh, Chang Rae Rho, Won-Kyung Cho, Seungbum Kang
Purpose: The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice. Methods: Choroidal neovascularization was induced by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27917718/the-role-of-rho-kinase-inhibitors-in-corneal-endothelial-dysfunction
#5
Naoki Okumura, Shigeru Kinoshita, Noriko Koizumi
BACKGROUND: The cornea is transparent tissue that serves as the window of the eye, allowing light to enter from the outer environment. The corneal endothelium maintains corneal transparency; thus, its dysfunction results in corneal haziness and causes severe vision loss. The only available therapeutic choice for treating corneal endothelial dysfunction has been transplantation using donor corneas; consequently, researchers have been pressed to develop new therapeutic options. METHODS: The goal of the review is to provide an overview of the research into Rho kinase (ROCK) inhibitors in the field of corneal endothelium therapy and the potential for clinical use of ROCK inhibitors...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27916091/-tryptase-inhibits-cell-apoptosis-through-upregulating-par-2-and-rho-kinase-in-rheumatoid-arthritis-synovial-fibroblasts
#6
Qianqian Zheng, Shigang Li, Yunli Jia, Wei Liu, Lingling Yu, Xianyong Chen, Jinling Wang
Objective To investigate the regulatory effects of tryptase on protease-activated receptors 2 (PAR-2), Rho signal pathway and apoptosis of MH7A rheumatoid arthritis synovial fibroblasts. Methods In MH7A cells, the expression of PAR-2 was measured by flow cytometry; cell apoptosis was examined by annexin V- FITC/PI staining combined with flow cytometry; the expression of Rho kinase was detected by Pull-down assay and Western botting. Results Tryptase upregulated the expression of PAR-2 in MH7A cells, and suppressed Fas-mediated apoptosis of MH7A cells in a dose-dependent manner...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27914611/restoration-of-uridine-5-triphosphate-suppressed-delayed-rectifying-k-currents-by-an-no-activator-kmup-1-involves-rhoa-rho-kinase-signaling-in-pulmonary-artery-smooth-muscle-cells
#7
Zen-Kong Dai, Chang-Ling Kao, Su-Ling Hsieh, Ing-Jun Chen, Bin-Nan Wu
We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca(2+) sensitivity, K(+)-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK) expression. This study further investigated whether KMUP-1 impedes uridine 5'-triphosphate (UTP)-inhibited delayed rectifying K(+) (KDR) current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat pulmonary arteries...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27914563/differential-effects-of-testosterone-and-estradiol-on-clitoral-function-an-experimental-study-in-rats
#8
Paolo Comeglio, Ilaria Cellai, Sandra Filippi, Chiara Corno, Francesca Corcetto, Annamaria Morelli, Elena Maneschi, Elisa Maseroli, Edoardo Mannucci, Massimiliano Fambrini, Mario Maggi, Linda Vignozzi
INTRODUCTION: Female sexual response is a complex phenomenon in which psychological, neurologic, and vascular mechanisms and hormonal factors interact. During the arousal phase, they cooperate to increase genital blood flow, thus inducing engorgement of the clitoris and lubrication of the vagina. Regulation of vascular and non-vascular smooth muscle tone is the crucial event in the erectile process. Preclinical studies have suggested that nitric oxide (NO) is the main vasodilator neurotransmitter modulating, through the second messenger cyclic guanosine monophosphate (cGMP), clitoral flow vessels...
December 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27911106/time-course-of-conjunctival-hyperemia-induced-by-a-rho-kinase-inhibitor-anti-glaucoma-eye-drop-ripasudil-0-4
#9
Etsuko Terao, Shunsuke Nakakura, Yasuko Fujisawa, Yuki Fujio, Kanae Matsuya, Yui Kobayashi, Hitoshi Tabuchi, Tsuyoshi Yoneda, Atsuki Fukushima, Yoshiaki Kiuchi
PURPOSE: We investigated the detailed time course of conjunctival hyperemia induced by ripasudil 0.4%, a novel Rho-kinase inhibitor anti-glaucoma eye drop, in healthy subjects. METHODS: We recruited 51 healthy subjects and administered ripasudil 0.4% in their right eye. We evaluated conjunctival hyperemia using slit lamp photography and measured the intraocular pressure (IOP) using the Icare PRO Rebound Tonometer at baseline and after 5, 15, 30, 60, 90, and 120 min...
December 2, 2016: Current Eye Research
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#10
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#11
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27904131/mir-31-regulates-rho-associated-kinase-myosin-light-chain-rock-mlc-pathway-and-inhibits-gastric-cancer-invasion-roles-of-rhoa
#12
Zhuo Chen, Shengnan Liu, Yuan Xia, Kejian Wu
BACKGROUND This study evaluated how the expression of miR-31 can be used to detect gastric cancer (GC) to help illuminate the role of miR-31 and RhoA in GC cells. MATERIAL AND METHODS We carried out our experiments using tissue specimens from 70 GC patients. The relative expression of miR-31 and RhoA mRNA in tissues and cells was detected by RT-PCR. The expression level of RhoA protein was detected by immunohistochemistry. GC cell line BGC-823 was transfected with six groups of vectors: blank group, NC (negative control) group, miR-31 mimics group, miR-31 mimics + RhoA group, miR-31 mimics + ROCK group, and miR-31 mimics + MLCK agonist group...
December 1, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27897119/glaucoma-hot-topics-in-pharmacology
#13
Shiama I Balendra, Parth Arvind Shah, Mishank Jain, Andrzej Grzybowski, Francesca M Cordeiro
BACKGROUND: Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods...
November 29, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27896306/data-for-increased-rho-kinase-activity-in-type-2-diabetic-patients
#14
Lei Liu, Lun Tan, Jinsheng Lai, Sheng Li, Dao Wen Wang
The data presented in this article are related to the research article entitled "Enhanced Rho-Kinase Activity: Pathophysiological Relevance in Type 2 Diabetes" [1]. Rho-Kinase has attracted a great deal of interest as a novel therapeutic target in cardiovascular diseases. These data describe the observed relationship of Rho-Kinase activity with type 2 diabetic patients. Rho-Kinase activity is determined by immunoblotting of peripheral blood leukocytes with the Phospho-Thr853 in the myosin-binding subunit of myosin light-chain phosphatase...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27892645/endothelial-cell-derived-endothelin-1-is-involved-in-abnormal-scar-formation-by-dermal-fibroblasts-through-rhoa-rho-kinase-pathway
#15
Koichiro Kiya, Tateki Kubo, Kenichiro Kawai, Shinsuke Matsuzaki, Rieko Muramatsu, Daisuke Maeda, Toshihiro Fujiwara, Akimitsu Nishibayashi, Shigeyuki Kanazawa, Kenji Yano, Genki Amano, Taiichi Katayama, Ko Hosokawa
Hypertrophic scars and keloids are characterized by excessive dermal deposition of extracellular matrix due to fibroblast-to-myofibroblast differentiation. Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells, and plays multiple roles in the wound-healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of ET-1 and involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid formation. We found that ET-1 expression on dermal microvascular endothelial cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin and mature scars...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27890480/chemerin-induced-arterial-contraction-is-gi-and-calcium-dependent
#16
David J Ferland, Emma S Darios, Richard R Neubig, Benita Sjögren, Nguyen Truong, Rosa Torres, Thomas S Dexheimer, Janice M Thompson, Stephanie W Watts
Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinetics of rat aortic smooth muscle cells to assess the possible signaling pathway. Chemerin-9 (nonapeptide of the chemerin S(157) isoform) caused a concentration-dependent contraction of isolated aorta (EC50 100nM) and elicited a concentration-dependent intracellular calcium response (EC50 10nM)...
November 24, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27886408/role-of-rock2-in-cd4-cells-in-allergic-airways-responses-in-mice
#17
David I Kasahara, Joel A Mathews, Fernanda M C Ninin, Allison P Wurmbrand, James K Liao, Stephanie A Shore
BACKGROUND: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration. OBJECTIVE: To determine the role of ROCK2 acting within CD4(+) cells in allergic airways responses. METHODS: ROCK2 haploinsufficient (ROCK2(+/-) ) and wildtype mice were sensitized with ovalbumin (OVA). ROCK2(+/-) mice then received either CD4(+) cells from ROCK2 sufficient OVA TCR transgenic (OT-II) mice or saline i...
November 25, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27882355/cullin-3-mutation-causes-arterial-stiffness-and-hypertension-through-a-vascular-smooth-muscle-mechanism
#18
Larry N Agbor, Stella-Rita C Ibeawuchi, Chunyan Hu, Jing Wu, Deborah R Davis, Henry L Keen, Frederick W Quelle, Curt D Sigmund
Cullin-3 (CUL3) mutations (CUL3Δ9) were previously identified in hypertensive patients with pseudohypoaldosteronism type-II (PHAII), but the mechanism causing hypertension and whether this is driven by renal tubular or extratubular mechanisms remains unknown. We report that selective expression of CUL3Δ9 in smooth muscle acts by interfering with expression and function of endogenous CUL3, resulting in impaired turnover of the CUL3 substrate RhoA, increased RhoA activity, and augmented RhoA/Rho kinase signaling...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27881665/local-pulsatile-contractions-are-an-intrinsic-property-of-the-myosin-2a-motor-in-the-cortical-cytoskeleton-of-adherent-cells
#19
Michelle A Baird, Neil Billington, Aibing Wang, Robert S Adelstein, James R Sellers, Robert S Fischer, Clare M Waterman
The role of non-muscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, however whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occur in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27881399/intradermal-administration-of-endothelin-1-attenuates-endothelium-dependent-and-independent-cutaneous-vasodilation-via-rho-kinase-in-young-adults
#20
Naoto Fujii, Tatsuro Amano, Lyra Halili, Jeffrey C Louie, Sarah Yan Zhang, Brendan D McNeely, Glen P Kenny
We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In twelve adults (25±6 years), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, 2000mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50mM sodium nitroprusside (20-25 min)...
November 23, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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