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https://www.readbyqxmd.com/read/28339093/rock-inhibition-as-a-potential-therapeutic-target-involved-in-apoptosis-in-hemangioma
#1
Ming-Ke Qiu, Shu-Qing Wang, Chang Pan, Yang Wang, Zhi-Wei Quan, Ying-Bin Liu, Jing-Min Ou
Gene expression was examined in hemangiomas (HA), benign, birthmark-like tumors occurring in infancy, and confirmed in HA-derived endothelial cells (HDEC), for which cell proliferation and apoptosis were also assessed. Protein and mRNA accumulation of Rho-associated protein kinase (ROCK), vascular endothelial growth factor (VEGF), Ki-67 and proliferating cell nuclear antigen was significantly higher in proliferating phase HAs than in involuting phase HAs. In contrast, p53 and caspase-3 exhibited higher levels of accumulation in involuting than proliferating HAs...
March 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28321011/vehicle-dependent-effects-of-sphingosine-1-phosphate-on-plasminogen-activator-inhibitor-1-expression
#2
Chiharu Takahashi, Makoto Kurano, Masako Nishikawa, Kuniyuki Kano, Tomotaka Dohi, Katsumi Miyauchi, Hiroyuki Daida, Tomo Shimizu, Junken Aoki, Yutaka Yatomi
AIM: Sphingosine 1-phosphate (S1P) has been suggested to be a positive regulator of plasminogen activator inhibitor 1 (PAI-1) in adipocytes, while some studies are not consistent with this prothrombotic property of S1P. Since S1P is bound to apolipoprotein M (apoM) on HDL or to albumin in plasma, we compared the properties of these two forms on the PAI-1 induction. METHODS: We investigated the associations of S1P, apoM, and PAI-1 concentrations in the plasma of normal coronary artery (NCA), stable angina pectoris (SAP), and acute coronary syndrome (ACS) subjects (n=32, 71, and 38, respectively)...
March 17, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28320516/l-f001-a-novel-multifunctional-rock-inhibitor-suppresses-neuroinflammation-in-vitro-and-in-vivo-involvement-of-nf-%C3%AE%C2%BAb-inhibition-and-nrf2-pathway-activation
#3
Jingkao Chen, Wei Yin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
Microglia and astrocytes are largely responsible for inflammatory injury in the brain of Alzheimer's disease (AD). Increasing evidence has indicated that Rho kinase (ROCK) plays an important role in the regulation of neuroinflammation. Previously, we synthesized a new chemical entity L-F001 and proved its potential inhibitory effects on ROCK and oxidative stress. Here, we investigated the anti-inflammatory effects and the molecular mechanisms of L-F001 in vitro and in vivo. L-F001 remarkably suppressed lipopolysaccharides (LPS)-elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as LPS-induced production of nitric oxide (NO), reactive oxygen species, interleukin-6 (IL-6) and tumor necreactive oxygen speciesis factor-α (TNF-α) in microglial BV-2 cells and in cultured astrocytes...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28317242/chemical-screening-identifies-rock-as-a-target-for-recovering-mitochondrial-function-in-hutchinson-gilford-progeria-syndrome
#4
Hyun Tae Kang, Joon Tae Park, Kobong Choi, Hyo Jei Claudia Choi, Chul Won Jung, Gyu Ree Kim, Young-Sam Lee, Sang Chul Park
Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent...
March 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#5
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28300846/regulation-of-rhoa-activity-by-the-cellular-prion-protein
#6
Hee-Jun Kim, Hong-Seok Choi, Jeong-Ho Park, Mo-Jong Kim, Hyoung-Gon Lee, Robert Bob Petersen, Yong-Sun Kim, Jae-Bong Park, Eun-Kyoung Choi
The cellular prion protein (PrP(C)) is a highly conserved glycosylphosphatidylinositol (GPI)-anchored membrane protein that is involved in the signal transduction during the initial phase of neurite outgrowth. The Ras homolog gene family member A (RhoA) is a small GTPase that is known to have an essential role in regulating the development, differentiation, survival, and death of neurons in the central nervous system. Although recent studies have shown the dysregulation of RhoA in a variety of neurodegenerative diseases, the role of RhoA in prion pathogenesis remains unclear...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28300565/the-shift-in-gh3-cell-shape-and-cell-motility-is-dependent-on-mlck-and-rock
#7
Dulce Ávila-Rodríguez, Carmen Solano Agama, Sirenia González-Pozos, Juan Vicente Méndez-Méndez, Alma Ortiz Plata, Laura Arreola-Mendoza, María E Mendoza-Garrido
Cytoskeletal organization, actin-myosin contractility and the cell membrane together regulate cell morphology in response to the cell environment, wherein the extracellular matrix (ECM) is an indispensable component. Plasticity in cell shape enables cells to adapt their migration mode to their surroundings. GH3 endocrine cells respond to different ECM proteins, acquiring different morphologies: a rounded on collagen I-III (C I-III) and an elongated on collagen IV (C IV). However, the identities of the molecules that participate in these responses remain unknown...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28288476/the-role-of-rho-rho-kinase-pathway-in-the-pathogenesis-of-cholesteatoma
#8
Mesut Yeşilova, Kemal Görür, Onur Ismi, Cengiz Özcan, Kansu Büyükafşar
OBJECTIVE: To assess the role of Rho/Rho-kinase pathway in the pathogenesis of cholesteatoma. MATERIALS AND METHODS: Thirty-eight patients with cholesteatoma, who had gone mastoidectomies were enrolled in this prospective study. Cholesteatomas matrix (CM) and a piece of the external ear canal skin (EECS as control) were taken and transferred to the liquid nitrogen and kept at -86 °C for Rho A and Rho-kinase (ROCK) analysis with Western blotting and commercial ELISA kits (Cell Biolabs Inc...
April 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28284975/chronic-treatment-with-taurine-after-intracerebroventricular-streptozotocin-injection-improves-cognitive-dysfunction-in-rats-by-modulating-oxidative-stress-cholinergic-functions-and-neuroinflammation
#9
K H Reeta, Devendra Singh, Y K Gupta
The present study investigated the neuroprotective effects of taurine, an essential amino acid for growth and development of central nervous system. Intracerebroventricular streptozotocin (ICV-STZ) model of cognitive impairment was used in male Wistar rats (270 ± 20 g). Morris water maze, elevated plus maze and passive avoidance paradigm were used to assess cognitive performance. Taurine (40, 60 and 120 mg/kg) was administered orally for 28 days following STZ administration on day 1. Oxidative stress parameters (malondialdehyde, glutathione, nitric oxide and superoxide dismutase) and cholinesterases (acetylcholinesterase and butyrylcholinesterase) activity were measured at end of the study in the cortex and hippocampus...
March 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28284330/inhibition-of-ages-rage-rho-rock-pathway-suppresses-non-specific-neuroinflammation-by-regulating-bv2-microglial-m1-m2-polarization-through-the-nf-%C3%AE%C2%BAb-pathway
#10
Jingkao Chen, Zhaowei Sun, Minghua Jin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28283529/targeting-the-rhoa-rock-pathway-to-reverse-t-cell-dysfunction-in-sle
#11
Cristina Rozo, Yurii Chinenov, Reena Khianey Maharaj, Sanjay Gupta, Laura Leuenberger, Kyriakos A Kirou, Vivian P Bykerk, Susan M Goodman, Jane E Salmon, Alessandra B Pernis
OBJECTIVES: Deregulated production of interleukin (IL)-17 and IL-21 contributes to the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Production of IL-17 and IL-21 can be regulated by ROCK2, one of the two Rho kinases. Increased ROCK activation was previously observed in an SLE cohort. Here, we evaluated ROCK activity in a new SLE cohort, and an RA cohort, and assessed the ability of distinct inhibitors of the ROCK pathway to suppress production of IL-17 and IL-21 by SLE T cells or human Th17 cells...
April 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28273942/human-corneal-endothelial-cell-cultivation-from-old-donor-corneas-with-forced-attachment
#12
Mohit Parekh, Sajjad Ahmad, Alessandro Ruzza, Stefano Ferrari
Human corneal endothelial cells (HCEnCs) are responsible for maintaining the transparency of the cornea. Damaged or diseased HCEnCs may cause blindness. Replacement of the diseased cells with a healthy donor endothelium is the only currently available treatment. Tissue-engineering can serve as an alternative to conventional donor corneal transplantation. Due to the global shortage of donor corneas, a wide interest in the development of cultured graft substitutes and artificial corneas has increased. Availability of the old donor corneas is higher especially for research...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270556/cytoskeletal-adaptivity-regulates-t-cell-receptor-signaling
#13
Timothy J Thauland, Kenneth H Hu, Marc A Bruce, Manish J Butte
The factors that govern T cell activation control the initiation and progression of adaptive immune responses. T cells recognize their cognate antigen on the surface of antigen-presenting cells (APCs) through the T cell receptor, which results in the formation of a contact region (immune synapse) between the two cells and the activation of the T cells. Activated T cells proliferate and differentiate into effector T cells that secrete cytokines, provide help to B cells, and kill target cells. We asked whether the actin cytoskeleton governs differences in signaling in effector T cells versus naïve (unstimulated) T cells...
March 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/28266583/zyz-168-alleviates-cardiac-fibrosis-after-myocardial-infarction-through-inhibition-of-erk1-2-dependent-rock1-activation
#14
Shanshan Luo, Tran Ba Hieu, Fenfen Ma, Ying Yu, Zhonglian Cao, Minjun Wang, Weijun Wu, Yicheng Mao, Peter Rose, Betty Yuen-Kwan Law, Yi Zhun Zhu
Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α-smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9)...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265821/suppression-of-rho-kinase-1-is-responsible-for-insulin-regulation-of-the-ampk-srebp-1c-pathway-in-skeletal-muscle-cells-exposed-to-palmitate
#15
Sunyinyan Tang, Wenjun Wu, Wenjuan Tang, Zhijuan Ge, Hongdong Wang, Ting Hong, Dalong Zhu, Yan Bi
AIMS: Clinical and experimental data suggest that early insulin therapy could reduce lipotoxicity in subjects and animal models with type 2 diabetes mellitus. However, the underlying mechanisms need to be clarified. Sterol regulatory element-binding protein 1c (SREBP-1c), which is negatively regulated by AMP-activated protein kinase (AMPK), plays a critical role in lipotoxicity and insulin resistance in skeletal muscle cells. Here, we investigated the effect and molecular mechanism of insulin intervention on the AMPK/SREBP-1c pathway in skeletal muscle cells with chronic exposure to palmitic acid (PA)...
March 7, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28260321/-hydroxyfasudi-attenuates-lipopolysaccharide-induced-endothelial-dysfunction-via-suppressing-the-expression-of-rho-associated-coiled-coil-protein-kinase-1-connexin-43-and-caveolin-1
#16
P F Zheng, X H Wu, W Huang, G T Ma, Q Bi
Objective: To investigate the effect and mechanism of hydroxyfasudi (HF), a specific Rho kinase inhibitor, on lipopolysaccharide(LPS)induced endothelial dysfunction. Methods: A total of 24 male Sprague Dawley rats were randomly divided into control group(n=6), HF group(n=6), LPS group(n=6) and LPS + HF group(n=6) with random number table method. There was no special treatment in control group. HF (30 mg/kg) was injected intraperitoneally in HF group. LPS (1 mg/kg) were injected intravenously in LPS group. In LPS+ HF group, HF (30 mg/kg) was injected intraperitoneally, followed by intravenous LPS injection (1 mg/kg) 30 minutes later...
February 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28259960/rock-actin-mrtf-signaling-promotes-the-fibrogenic-phenotype-of-fibroblast-like-synoviocytes-derived-from-the-temporomandibular-joint
#17
Seiji Yokota, Naoyuki Chosa, Seiko Kyakumoto, Hitomichi Kimura, Miho Ibi, Masaharu Kamo, Kazuro Satoh, Akira Ishisaki
Malocclusion caused by abnormal jaw development or muscle overuse during mastication results in abnormal mechanical stress to the tissues surrounding the temporomandibular joint (TMJ). Excessive mechanical stress against soft and hard tissues around the TMJ is involved in the pathogenesis of inflammatory diseases, including osteoarthritis (OA). OA-related fibrosis is a possible cause of joint stiffness in OA. However, cellular and molecular mechanisms underlying fibrosis around the TMJ remain to be clarified...
February 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28259907/o-glcnacylation-promotes-migration-and-invasion-in-human-ovarian-cancer-cells-via-the-rhoa-rock-mlc-pathway
#18
Yichao Niu, Ye Xia, Jingyun Wang, Xiaofei Shi
O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. The addition and removal of O‑Linked β-N-acetylglucosamine (O‑GlcNAc) on target proteins is catalyzed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively. Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O‑GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet‑G...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28251925/the-rhogap-protein-arhgap18-senex-localises-to-microtubules-and-regulates-their-stability-in-endothelial-cells
#19
Michael D Lovelace, Elizabeth E Powter, Paul R Coleman, Yang Zhao, Amelia Parker, Garry H Chang, Angelina J Lay, Julie Hunter, Aaron P McGrath, Mika Jormakka, Patrick Bertolino, Geoffrey McCaughan, Maria Kavallaris, Mathew A Vadas, Jennifer R Gamble
RhoGTPases are important regulators of the cell cytoskeleton, controlling cell shape, migration and proliferation. Previously, we showed ARHGAP18 in endothelial cells is important in cell junctions. Here we show using structured illumination microscopy (SIM), ground state depletion (GSD) and total internal reflection fluorescence (TIRF) that a proportion of ARHGAP18 localises to microtubules in endothelial cells as well as non-endothelial cells, an association confirmed biochemically. In endothelial cells some ARHGAP18 puncta also colocalised to Weibel-Palade Bodies on the microtubules...
March 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28241317/tgf%C3%AE-2-induces-the-formation-of-cross-linked-actin-networks-clans-in-human-trabecular-meshwork-cells-through-the-smad-and-non-smad-dependent-pathways
#20
Michela Montecchi-Palmer, Jaclyn Y Bermudez, Hannah C Webber, Gaurang C Patel, Abbot F Clark, Weiming Mao
Purpose: Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including the formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in the AH and TM of primary open angle glaucoma (POAG) patients and induces POAG-associated TM changes, including CLANs. We determined the role of individual TGFβ2 signaling pathways in CLAN formation. Methods: Cultured nonglaucomatous human TM (NTM) cells were treated with control or TGFβ2, with or without the inhibitors of TGFβ receptor, Smad3, c-Jun N-terminal kinases (JNK), extracellular signal regulated kinase (ERK), P38, or Rho-associated protein kinase (ROCK)...
February 1, 2017: Investigative Ophthalmology & Visual Science
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