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Rock inhibitor

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https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#1
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/27917718/the-role-of-rho-kinase-inhibitors-in-corneal-endothelial-dysfunction
#2
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/27917311/rock-inhibition-promotes-attachment-proliferation-and-wound-closure-in-human-embryonic-stem-cell-derived-retinal-pigmented-epithelium
#3
Roxanne H Croze, William J Thi, Dennis O Clegg
PURPOSE: Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD...
November 2016: Translational Vision Science & Technology
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
#4
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
#5
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/27904131/mir-31-regulates-rho-associated-kinase-myosin-light-chain-rock-mlc-pathway-and-inhibits-gastric-cancer-invasion-roles-of-rhoa
#6
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/27894406/vincristine-promotes-migration-and-invasion-of-colorectal-cancer-hct116-cells-through-rhoa-rock-myosin-light-chain-pathway
#7
X Jin, K Liu, B Jiao, X Wang, S Huang, W Ren, K Zhao
Vincristine is an antitumor vinca alkaloid isolated from vinca rosea, and is a medication used to treat a number of types of cancer. In this study, we investigated the impact of vincristine on oncogenic phenotypes of human colorectal cancer HCT116 cells. MTT assay demonstrated that vincristine showed a obviously inhibitory effect on cell growth compared to non-treated cells. However, Transwell assay showed that vincristine promoted migration and invasion of HCT116 cells in vitro in a concentration-dependent manner between 0...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27886408/role-of-rock2-in-cd4-cells-in-allergic-airways-responses-in-mice
#8
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/27885213/a-fret-biosensor-for-rock-based-on-a-consensus-substrate-sequence-identified-by-kiss-technology
#9
Chunjie Li, Ayako Imanishi, Naoki Komatsu, Kenta Terai, Mutsuki Amano, Kozo Kaibuchi, Michiyuki Matsuda
Genetically-encoded biosensors based on Förster/fluorescence resonance energy transfer (FRET) are versatile tools for studying the spatio-temporal regulation of signaling molecules within not only the cells but also tissues. Perhaps the hardest task in the development of a FRET biosensor for protein kinases is to identify the kinase-specific substrate peptide to be used in the FRET biosensor. To solve this problem, we took advantage of kinase-interacting substrate screening (KISS) technology, which deduces a consensus substrate sequence for the protein kinase of interest...
November 23, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27880913/mdia-and-rock-mediate-actin-dependent-presynaptic-remodeling-regulating-synaptic-efficacy-and-anxiety
#10
Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Daisuke Yamada, Masayuki Sekiguchi, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya
Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879448/rhoa-kinase-inhibition-with-fasudil-versus-simvastatin-in-murine-models-of-cerebral-cavernous-malformations
#11
Robert Shenkar, Changbin Shi, Cecilia Austin, Thomas Moore, Rhonda Lightle, Ying Cao, Lingjiao Zhang, Meijing Wu, Hussein A Zeineddine, Romuald Girard, David A McDonald, Autumn Rorrer, Carol Gallione, Peter Pytel, James K Liao, Douglas A Marchuk, Issam A Awad
BACKGROUND AND PURPOSE: We sought to compare the effect of chronic treatment with commonly tolerated doses of Fasudil, a specific RhoA kinase (ROCK) inhibitor, and simvastatin (with pleiotropic effects including ROCK inhibition) on cerebral cavernous malformation (CCM) genesis and maturation in 2 models that recapitulate the human disease. METHODS: Two heterozygous murine models, Ccm1(+/-)Msh2(-)(/-) and Ccm2(+/-)Trp53(-/-), were treated from weaning to 4 to 5 months of age with Fasudil (100 mg/kg per day), simvastatin (40 mg/kg per day) or with placebo...
November 22, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27847705/a-model-of-glial-scarring-analogous-to-the-environment-of-a-traumatically-injured-spinal-cord-using-kainate
#12
Jong Yoon Yoo, Chang Ho Hwang, Hea Nam Hong
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM)...
October 2016: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/27846787/cryopreservation-of-brain-endothelial-cells-derived-from-human-induced-pluripotent-stem-cells-is-enhanced-by-rock-inhibition
#13
Hannah Kathryn Wilson, Madeline G Faubion, Michael K Hjortness, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) maintains brain homeostasis but also presents a major obstacle to brain drug delivery. Brain microvascular endothelial cells (BMECs) form the principal barrier and therefore represent the major cellular component of in vitro BBB models. Such models are often used for mechanistic studies of the BBB in health and disease and for drug screening. Recently, human induced pluripotent stem cells (iPSCs) have emerged as a new source for generating BMEC-like cells for use in in vitro human BBB studies...
November 15, 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27830013/dihydrotestosterone-modulates-endothelial-progenitor-cell-function-via-rhoa-rock-pathway
#14
Hao Zhang, Liang Shi, Guo-Qing Ren, Wen-Wen Sun, Yi-Bin Wang, Yi-Kun Chen, Jiang-Ning Yin, Bing Wan
BACKGROUND: Previous findings indicate that testosterone level is negatively correlated with the incidence and mortality of cardiovascular diseases in men. Endothelial progenitor cells (EPCs) play a critical role in endothelial healing and vascular integrity. This study aimed to examine the effects of dihydrotestosterone (DHT), an active metabolite of testosterone, on human EPC function and investigate the underlying mechanism. METHODS: EPCs were isolated from peripheral blood of healthy adult males and incubated with a series of concentrations (1, 10, and 100 nmol/L in dimethyl sulfoxide) of DHT for 24 h or with 10 nmol/L DHT for different periods (6, 12, 24, 36, and 48 h)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27825961/repression-of-microrna-function-mediates-inflammation-associated-colon-tumorigenesis
#15
Takeshi Yoshikawa, Jianfeng Wu, Motoyuki Otsuka, Takahiro Kishikawa, Nobumi Suzuki, Akemi Takata, Motoko Ohno, Rei Ishibashi, Mari Yamagami, Ryo Nakagawa, Naoya Kato, Masaaki Miyazawa, Jiahuai Han, Kazuhiko Koike
BACKGROUND & AIMS: Little is known about the mechanisms by which chronic inflammation contributes to carcinogenesis, such as the development of colon tumors in patients with inflammatory bowel diseases. Specific microRNA (miRNAs) can function as suppressors or oncogenes, and widespread alterations in miRNA expression have been associated with tumorigenesis. We studied whether alterations in miRNA function contribute to inflammation-associated colon carcinogenesis. METHODS: We studied the effects of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1 alpha (IL1A), and IL1 beta (IL1B) on miRNA function, measured by activity of reporter constructs containing miRNA-binding sites in their 3' untranslated regions, in human 293T embryonic kidney, Caco-2, HT29, and HCT116 colon carcinoma cells, as well as dicer +/+ and dicer -/- and Apobec3 +/+ and Apobec3 -/- mouse embryonic fibroblasts...
November 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27825172/oxidized-low-density-lipoprotein-induced-cyclophilin-a-secretion-requires-rock-dependent-diphosphorylation-of-myosin-light-chain
#16
Zizhuo Su, Rongjie Lin, Yuyang Chen, Xiaorong Shu, Haifeng Zhang, Shumin Liang, Ruqiong Nie, Jingfeng Wang, Shuanglun Xie
OBJECTIVE: Accumulation of cyclophilin A (CyPA) within atherosclerotic lesions is thought to be implicated in the progression of atherosclerosis. However, the source of CyPA within atherosclerotic lesions is still unknown. The aim of this study is to determine the role of oxidized low-density lipoproteins (ox-LDL) in vascular smooth muscle cell (VSMC)-derived CyPA secretion and the underlying mechanism. METHODS AND RESULTS: Abundant CyPA and α-smooth muscle actin (α-SMA) expressed in atherosclerotic lesions was observed in apolipoprotein E-deficient mice...
November 9, 2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27799301/anoctamin-6-contributes-to-cl-secretion-in-accessory-cholera-enterotoxin-ace-stimulated-diarrhea-an-essential-role-for-pip2-signaling-in-cholera
#17
Joydeep Aoun, Mikio Hayashi, Irshad Ali Sheikh, Paramita Sarkar, Tultul Saha, Priyanka Ghosh, Rajsekhar Bhowmick, Dipanjan Ghosh, Tanaya Chatterjee, Pinak Chakrabarti, Manoj K Chakrabarti, Kazi Mirajul Hoque
Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea However, the signaling mechanism and specific type of Cl- channel activated by Ace is yet unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane which were inhibited by classical CaCC blockers. Surprisingly, Ace elicited rise of current was neither affected by Ano1 (Tmem16a) specific inhibitor T16A(inh)-AO1(TAO1) nor by CFTR blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27791202/fasudil-an-inhibitor-of-rho-associated-coiled-coil-kinase-improves-cognitive-impairments-induced-by-smoke-exposure
#18
Deng Xueyang, Ma Zhanqiang, Ma Chunhua, Hao Kun
The current study was designed to investigate the pathological changes in brain induced by smoke exposure, and explore whether fasudil could alleviate these impairments.Adult C57BL/6 mice were exposed to tobacco smoking for four months, and fasudil was treated from the third months. To investigate lung injuries, the immunohistochemistry of lung tissue, immune cell infiltrations, cytokine productions in bronchoalveolar lavage (BAL) fluid, and seurm inflammatory cytokines were evaluated. To investigate cognitive impairments, Morris water maze test, hippocampal inflammatory cytokines and Rho associated signaling pathways were evaluated...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27768934/the-proteasome-regulates-collagen-induced-platelet-aggregation-via-nuclear-factor-kappa-b-nf%C3%A4-b-activation
#19
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27763717/additive-effects-of-the-rho-kinase-inhibitor-y-27632-and-vardenafil-on-relaxation-of-the-corpus-cavernosum-tissue-of-patients-with-erectile-dysfunction-and-clinical-phosphodiesterase-type-5-inhibitor-failure
#20
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk J M K De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR])...
October 20, 2016: BJU International
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