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https://www.readbyqxmd.com/read/28929640/rho-kinase-inhibitor-fasudil-attenuates-contrast-induced-acute-kidney-injury
#1
Yiming Wang, Hao Zhang, Zhijian Yang, Dengshun Miao, Dingguo Zhang
In this study, we tested the hypothesis that fasudil, a Rho kinase inhibitor, would protect against contrast-induced acute kidney injury (CI-AKI) in a mouse model and attempted to elucidate the mechanism involved. Mice subjected to unilateral ligation of the left anterior renal pedicle were divided into four groups: (1) control group, (2) CI-AKI induced by contrast media (CM group), (3) CI-AKI plus low-dose fasudil (LD group) and (4) CI-AKI plus high-dose fasudil (HD group). Animals from groups 2-4 received iodixanol (4...
September 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28926926/protective-effects-of-aloperin-on-monocroline-induced-pulmonary-hypertension-via-regulation-of-rho-a-rho-kinsase-pathway-in-rats
#2
Fan Wu, Wanxia Yao, Jiamei Yang, Min Zhang, Yanping Xu, Yinju Hao, Lin Yan, Yang Niu, Tao Sun, Jianqiang Yu, Ru Zhou
Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#3
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#4
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28914001/comparative-study-of-the-effects-of-trabecular-meshwork-outflow-drugs-on-the-permeability-and-nitric-oxide-production-in-trabecular-meshwork-cells
#5
Jae Woo Kim
PURPOSE: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayer and the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors, adenosine, and statin. METHODS: Primary cultured TM cells were exposed to 10 or 25 μM Y-27632, 0.1 or 1 μM N6-cyclohexyladenosine (CHA), or 15 or 30 μM simvastatin for 24 hours. NO production and expression of endothelial nitric oxide synthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively...
July 25, 2017: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/28893104/ripasudil-hydrochloride-hydrate-targeting-rho-kinase-in-the-treatment-of-glaucoma
#6
Toshihiro Inoue, Hidenobu Tanihara
Among the intraocular pressure (IOP)-lowering drugs used in a clinical setting, Rho kinase (ROCK) inhibitors lower IOP by a unique mechanism, namely the depolymerization of intracellular actin in the conventional outflow tissues: the trabecular meshwork (TM) and Schlemm's canal (SC). Furthermore, ROCK inhibitors suppress the production of extracellular matrix by TM cells, which represents a potential alternative method of lowering IOP. Considering that conventional outflow is a dominant pathway in humans, IOP-lowering ROCK inhibitors, delivered in conjunction with other drugs, may be able to treat the glaucomatous eye...
September 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28886159/directional-migration-of-mesenchymal-stem-cells-under-an-sdf-1%C3%AE-gradient-on-a-microfluidic-device
#7
Siwan Park, Hwanseok Jang, Byung Soo Kim, Changmo Hwang, Gi Seok Jeong, Yongdoo Park
Homing of peripheral stem cells is regulated by one of the most representative homing factors, stromal cell-derived factor 1 alpha (SDF-1α), which specifically binds to the plasma membrane receptor CXCR4 of mesenchymal stem cells (MSCs) in order to initiate the signaling pathways that lead to directional migration and homing of stem cells. This complex homing process and directional migration of stem cells have been mimicked on a microfluidic device that is capable of generating a chemokine gradient within the collagen matrix and embedding endothelial cell (EC) monolayers to mimic blood vessels...
2017: PloS One
https://www.readbyqxmd.com/read/28885066/nanoparticle-size-specific-actin-rearrangement-and-barrier-dysfunction-of-endothelial-cells
#8
Yizhong Liu, Noga Rogel, Kei Harada, Leigha Jarett, Christopher H Maiorana, Guy K German, Gretchen J Mahler, Amber L Doiron
In this work, we evaluated the impact of gold nanoparticles on endothelial cell behavior and function beyond the influence on cell viability. Five types of gold nanoparticles were studied: 5 nm and 20 nm bare gold nanoparticles, 5 nm and 20 nm gold nanoparticles with biocompatible polyethylene glycol (PEG) coating and 60 nm bare gold nanoparticles. We found that all tested gold nanoparticles did not affect cell viability significantly and reduced the reactive oxygen species (ROS) level in endothelial cells...
September 8, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28882559/enhancement-of-s1p-induced-contractile-response-in-detrusor-smooth-muscle-of-rats-having-cystitis
#9
Irfan Anjum, Merve Denizalti, Hilmi Burak Kandilci, Nezahat Tugba Durlu-Kandilci, Inci Sahin-Erdemli
Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis...
September 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28881850/transforming-growth-factor-%C3%AE-a-potential-biomarker-and-therapeutic-target-of-ventricular-remodeling
#10
REVIEW
Yuan Ma, Hai Zou, Xing-Xing Zhu, Jie Pang, Qiang Xu, Qin-Yang Jin, Ya-Hui Ding, Bing Zhou, Dong-Sheng Huang
Transforming growth factor β (TGF-β) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-β receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-β in VR and suggest potential therapeutic targets of the TGF-β signaling pathways for VR...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881620/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#11
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#12
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28841413/the-tropism-of-pleiotrophin-orchestrating-glioma-brain-invasion
#13
COMMENT
David H Gutmann
The lateral ventricle (LV) is a preferential location for brain tumor spread; however, the instructive cues responsible for this unique tropism were previously unknown. In this issue, Qin et al. elucidate the underlying mechanism, demonstrating that LV-neural progenitors secrete a pleiotrophin (PTN)-containing complex, which attracts glioma cells through ROCK/Rho activation.
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28840514/g%C3%AE-q-p63rhogef-interaction-in-rhoa-rho-kinase-signaling-investigation-in-gitelman-s-syndrome-and-implications-with-hypertension
#14
E Pagnin, V Ravarotto, G Maiolino, E Naso, P A Davis, L A Calò
PURPOSE: Gitelman's syndrome (GS) presents normo-hypotension and absence of cardiovascular-renal remodeling despite high angiotensin II (Ang II), activation of renin-angiotensin-aldosterone system and is a human model of endogenous antagonism of Ang II signaling, opposite to hypertension. GS's clinical presentation leads to questions regarding what features might be responsible. One area of investigation involves Ang II signaling. In hypertensive patients, RhoA/Rho kinase (RhoA/ROCK) pathway activation by Ang II is involved in hypertension development/maintenance and induction of long-term consequences (cardiovascular-renal remodeling), while GS has reduced p63RhoGEF gene and protein levels and ROCK activity...
August 24, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#15
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820400/alteration-in-expressions-of-rhoa-and-rho-kinases-during-pregnancy-in-rats-their-roles-in-uterine-contractions-and-onset-of-labour
#16
D Domokos, E Ducza, G Falkay, R Gaspar
Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis. The other purpose was to evaluate the effects of the ROCK (Y-27632, fasudil and RKI 1441) and RhoA inhibitors (simvastatin) on uterine contractility in isolated organ bath experiments...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819898/regulation-of-hepatic-na-k-atpase-in-obese-female-and-male-rats-involvement-of-erk1-2-ampk-and-rho-rock
#17
Julijana Stanimirovic, Milan Obradovic, Anastasija Panic, Voin Petrovic, Dragan Alavantic, Irena Melih, Esma R Isenovic
In this study, we assessed whether the disturbed regulation of sodium/potassium-adenosine-triphosphatase (Na(+)/K(+)-ATPase) occurs as a consequence of obesity-induced IR in sex-specific manner. We also assessed whether alterations of IRS/PI3K/Akt, ERK1/2, AMPKα, and RhoA/ROCK signaling cascades have an important role in this pathology. Female and male Wistar rats (150-200 g, 8 weeks old) were fed a standard laboratory diet or a high-fat (HF) diet (42% fat) for 10 weeks. The activity of hepatic Na(+)/K(+)-ATPase and Rho, and the association of IRS-1/p85 were assessed in liver...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28819566/development-of-poly-lactic-glycolic-acid-plga-microspheres-for-controlled-release-of-rho-associated-kinase-inhibitor
#18
Sho Koda, Naoki Okumura, Junji Kitano, Noriko Koizumi, Yasuhiko Tabata
PURPOSE: The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. METHOD: ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28810542/electroacupuncture-promotes-axonal-regeneration-in-rats-with-focal-cerebral-ischemia-through-the-downregulation-of-nogo-a-ngr-rhoa-rock-signaling
#19
Saie Huang, Danxia Huang, Jiapei Zhao, Lidian Chen
The purpose of the present study was to evaluate the effect of electroacupuncture (EA) on the axonal regeneration environment following cerebral ischemia injury and to investigate whether it was associated with Nogo-A/Nogo receptor (NgR)/RhoA/Rho-associated protein kinase (ROCK) signaling. Using a rat model of focal cerebral ischemia, the effects of EA at the Quchi (LI11) and Zusanli (ST36) acupoints on axonal growth inhibitory protein and axonal growth factors were assessed and the underlying molecular mechanisms were investigated...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28804108/effects-of-vitrification-and-a-rho-associated-coiled-coil-containing-protein-kinase-1-inhibitor-on-the-meiotic-and-developmental-competence-of-feline-oocytes
#20
Saengtawan Arayatham, Narong Tiptanavattana, Theerawat Tharasanit
Oocyte cryopreservation is the technique of choice for the long-term storage of female gametes. However, it induces an irreversible loss of oocyte viability and function. We examined the effects of vitrification and a Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibitor (ROCKi) on the meiotic and developmental competence of feline oocytes. We examined the expression of LIM kinase (LIMK) 1 and 2, with and without ROCKi treatment. Cumulus oocyte complexes (COCs) were matured in vitro with 0, 10, 20, and 40 µM ROCKi...
August 11, 2017: Journal of Reproduction and Development
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