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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
#1
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
#2
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
#3
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
#4
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/28803065/flow-induced-adherens-junction-remodeling-driven-by-cytoskeletal-forces
#5
Deepika Verma, Vivek Bajpai, Nannan Ye, Mohammad M Maneshi, Deekshitha Jetta, Stelios T Andreadis, Frederick Sachs, Susan Z Hua
Adherens junctions (AJs) are a key structural component for tissue organization and function. Under fluid shear stress, AJs exhibit dynamic assembly/disassembly, but how shear stress couples to AJs is unclear. In MDCK cells we measured simultaneously the forces in cytoskeletal α-actinin and the density and length of AJs using a genetically coded optical force sensor, actinin-sstFRET, and fluorescently labeled E-cadherin (E-cad). We found that shear stress of 0.74dyn/cm(2) for 3hours significantly enhanced E-cad expression at cell-cell contacts and this phenomenon has two phases...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#6
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28794110/involvement-of-connexin43-phosphorylation-and-gap-junctional-communication-in-vasopressin-induced-rock-dependent-vasoconstriction-after-hemorrhagic-shock
#7
Guangming Yang, Xiaoyong Peng, Yue Wu, Tao Li, Liangming Liu
We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock, and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia...
August 9, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28794073/rock-inhibitors-for-the-treatment-of-ocular-diseases
#8
REVIEW
Ramin Nourinia, Shintaro Nakao, Souska Zandi, Sare Safi, Ali Hafezi-Moghadam, Hamid Ahmadieh
The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of multiple ocular and systemic disorders. Recently, ROCK inhibitors have been suggested as novel treatments for various ocular diseases. Several in vitro, in vivo and clinical studies have demonstrated the safety and efficacy of ROCK inhibitors in the management of ocular disorders such as corneal epithelial and endothelial damage, glaucoma, retinal and choroidal neovascularisation, diabetic macular oedema and optic nerve disorders...
August 9, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28793244/rho-associated-kinases-and-non-muscle-myosin-iis-inhibit-the-differentiation-of-human-ipscs-to-pancreatic-endoderm
#9
Taro Toyoda, Azuma Kimura, Hiromi Tanaka, Tomonaga Ameku, Atsushi Mima, Yurie Hirose, Masahiro Nakamura, Akira Watanabe, Kenji Osafune
There has been increasing success with the generation of pancreatic cells from human induced pluripotent stem cells (hiPSCs); however, the molecular mechanisms of the differentiation remain elusive. The purpose of this study was to reveal novel molecular mechanisms for differentiation to PDX1(+)NKX6.1(+) pancreatic endoderm cells, which are pancreatic committed progenitor cells. PDX1(+) posterior foregut cells differentiated from hiPSCs failed to differentiate into pancreatic endoderm cells at low cell density, but Rho-associated kinase (ROCK) or non-muscle myosin II (NM II) inhibitors rescued the differentiation potential...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28793219/stiff-substrates-increase-inflammation-induced-endothelial-monolayer-tension-and-permeability
#10
Rebecca Lownes Urbano, Christina Furia, Sarah Basehore, Alisa Morss Clyne
Arterial stiffness and inflammation are associated with atherosclerosis, and each have individually been shown to increase endothelial monolayer tension and permeability. The objective of this study was to determine if substrate stiffness enhanced endothelial monolayer tension and permeability in response to inflammatory cytokines. Porcine aortic endothelial cells were cultured at confluence on polyacrylamide gels of varying stiffness and treated with either tumor necrosis factor-α (TNFα) or thrombin. Monolayer tension was measured through vinculin localization at the cell membrane, traction force microscopy, and phosphorylated myosin light chain quantity and actin fiber colocalization...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28782712/effects-of-fasudil-on-pulmonary-hypertension-in-clinical-practice
#11
REVIEW
Yiqing Zhang, Shangjie Wu
Pulmonary hypertension (PH) is a pathophysiologic disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. The presence of PH is associated with worse outcomes, but the efficacy of current therapy is still unsatisfactory. Because Rho-kinase (ROCK) plays an important role in the pathogenesis of PH, the ROCK inhibitor fasudil is expected to contribute to PH treatment. In animal models of PH, fasudil reduced pulmonary artery pressure (PAP) and improved survival...
August 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28751979/application-of-rho-kinase-inhibitors-for-the-treatment-of-corneal-endothelial-diseases
#12
REVIEW
Naoki Okumura, Shigeru Kinoshita, Noriko Koizumi
ROCK (Rho kinase) signaling regulates a wide spectrum of fundamental cellular events and is involved in a variety of pathological conditions. It has therefore attracted research interest as a potential therapeutic target for combating various diseases. We showed that inhibition of ROCK enhances cell proliferation, promotes cell adhesion onto a substrate, and suppresses apoptosis of corneal endothelial cells (CECs). In addition, we reported that a ROCK inhibitor enhances wound healing in the corneal endothelium in animal models and in pilot clinical research...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28751650/rhoa-phosphorylation-mediated-by-rho-rhoa-associated-kinase-pathway-improves-the-anti-freezing-potentiality-of-murine-hatched-and-diapaused-blastocysts
#13
Meichao Gu, Hemin Ni, Xihui Sheng, Alfredo Pauciullo, Yunhai Liu, Yong Guo
Embryonic cryopreservation has a relatively low survival rate because of cytoskeletal damage. However, molecular anti-freezing mechanisms have been largely unexplored. This study investigated the significance of RhoA, involved in embryonic development, and the Rho/RhoA-associated kinase (ROCK) signalling pathway in cryopreservation. The anti-freezing mechanism in murine dormant embryos, compared with normal blastocysts, was assessed by combining molecular, physiological and pharmacological approaches. Real-time PCR and western blotting experiments showed high RhoA expression in cryo-dormant and dormant embryos...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#14
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28737169/actomyosin-drives-cancer-cell-nuclear-dysmorphia-and-threatens-genome-stability
#15
Tohru Takaki, Marco Montagner, Murielle P Serres, Maël Le Berre, Matt Russell, Lucy Collinson, Karoly Szuhai, Michael Howell, Simon J Boulton, Erik Sahai, Mark Petronczki
Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28732351/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#16
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#17
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28722749/rho-associated-protein-kinases-as-therapeutic-targets-for-both-vascular-and-parenchymal-pathologies-in-alzheimer-s-disease
#18
REVIEW
Aaron Y Lai, JoAnne McLaurin
The causes of late-onset Alzheimer's disease are unclear and likely multifactorial. Rho-associated protein kinases (ROCKs) are ubiquitously expressed signaling messengers that mediate a wide array of cellular processes. Interestingly, they play an important role in several vascular and brain pathologies implicated in Alzheimer's etiology, including hypertension, hypercholesterolemia, blood-brain barrier disruption, oxidative stress, deposition of vascular and parenchymal amyloid-beta peptides, tau hyperphosphorylation, and cognitive decline...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722478/rho-kinase-inhibitors-from-adlay-seeds
#19
Yhiya Amen, Qinchang Zhu, Hai-Bang Tran, Mohamed S Afifi, Ahmed F Halim, Ahmed Ashour, Ryoji Fujimoto, Takahiro Goto, Kuniyoshi Shimizu
Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds...
July 19, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28709411/rho-kinase-proteins-display-aberrant-upregulation-in-vascular-tumors-and-contribute-to-vascular-tumor-growth
#20
Clarissa N Amaya, Dianne C Mitchell, Brad A Bryan
BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells...
July 14, 2017: BMC Cancer
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