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https://www.readbyqxmd.com/read/28317242/chemical-screening-identifies-rock-as-a-target-for-recovering-mitochondrial-function-in-hutchinson-gilford-progeria-syndrome
#1
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
#2
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/28287465/serine-threonine-kinase-3-phosphoinositide-dependent-protein-kinase-1-pdk1-as-a-key-regulator-of-cell-migration-and-cancer-dissemination
#3
REVIEW
Laura Di Blasio, Paolo A Gagliardi, Alberto Puliafito, Luca Primo
Dissecting the cellular signaling that governs the motility of eukaryotic cells is one of the fundamental tasks of modern cell biology, not only because of the large number of physiological processes in which cell migration is crucial, but even more so because of the pathological ones, in particular tumor invasion and metastasis. Cell migration requires the coordination of at least four major processes: polarization of intracellular signaling, regulation of the actin cytoskeleton and membrane extension, focal adhesion and integrin signaling and contractile forces generation and rear retraction...
March 11, 2017: Cancers
https://www.readbyqxmd.com/read/28284870/identification-of-a-new-class-of-potent-cdc7-inhibitors-designed-by-putative-pharmacophore-model-synthesis-and-biological-evaluation-of-2-3-dihydrothieno-3-2-d-pyrimidin-4-1h-ones
#4
Osamu Kurasawa, Yuya Oguro, Tohru Miyazaki, Misaki Homma, Kouji Mori, Kenichi Iwai, Hideto Hara, Robert Skene, Isaac Hoffman, Akihiro Ohashi, Sei Yoshida, Tomoyasu Ishikawa, Nobuo Cho
Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety...
February 16, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28279687/airborne-particulate-matter-in-vitro-exposure-induces-cytoskeleton-remodeling-through-activation-of-the-rock-mypt1-mlc-pathway-in-a549-epithelial-lung-cells
#5
Yolanda I Chirino, Claudia María García-Cuellar, Carlos García-García, Ernesto Soto-Reyes, Álvaro Román Osornio-Vargas, Luis A Herrera, Alejandro López-Saavedra, Javier Miranda, Raúl Quintana-Belmares, Irma Rosas Pérez, Yesennia Sánchez-Pérez
Airborne particulate matter with an aerodynamic diameter ≤10μm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10 exposure in A549 lung epithelial cells...
March 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28266583/zyz-168-alleviates-cardiac-fibrosis-after-myocardial-infarction-through-inhibition-of-erk1-2-dependent-rock1-activation
#6
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
#7
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
#8
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/28225457/rhoa-rock-pathway-inhibition-by-fasudil-suppresses-the-vasculogenic-mimicry-of-u2os-osteosarcoma-cells-in-vitro
#9
Yun Xia, Xianyi Cai, Jiquan Fan, Liling Zhang, Zhenyu Li, Jinghua Ren, Gang Wu, Fang Zhu
GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) - a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1...
February 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28225294/role-of-rock-isoforms-in-regulation-of-stiffness-induced-myofibroblast-differentiation-in-lung-fibrosis
#10
Su S Htwe, Byung H Cha, Kan Yue, Ali Khademhosseini, Alan J Knox, Amir M Ghaemmaghami
Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibrotic state. There are two known ROCK isoforms in human, ROCK1 (ROKβ) and ROCK2 (ROKα), but specific role of each isoform in myofibroblast differentiation in lung fibrosis remains unknown. To study this, we developed a Gelatin methacryloyl (GelMA) hydrogel based culture system with different stiffness levels relevant to healthy and fibrotic lungs...
February 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28205334/long-non-coding-rna-tug1-promotes-migration-and-invasion-by-acting-as-a-cerna-of-mir-335-5p-in-osteosarcoma-cells
#11
Yong Wang, Tao Yang, Zhen Zhang, Ming Lu, Wei Zhao, Xiandong Zeng, Weiguo Zhang
Long non-coding RNAs (lncRNAs) have now become the new hotspots in an ocean of diseases including osteosarcoma. The function of taurine up-regulated gene 1 (TUG1) and its working mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. Also, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma...
February 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28191820/vascular-smooth-muscle-cell-glycocalyx-mediates-shear-stress-induced-contractile-responses-via-a-rho-kinase-rock-myosin-light-chain-phosphatase-mlcp-pathway
#12
Hongyan Kang, Jiajia Liu, Anqiang Sun, Xiao Liu, Yubo Fan, Xiaoyan Deng
The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm(2)) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28188861/functions-of-rho-family-of-small-gtpases-and-rho-associated-coiled-coil-kinases-in-bone-cells-during-differentiation-and-mineralization
#13
REVIEW
Agnieszka Strzelecka-Kiliszek, Saida Mebarek, Monika Roszkowska, René Buchet, David Magne, Slawomir Pikula
BACKGROUND: Members of Rho-associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM). SCOPE OF THE REVIEW: Here, we focus on the action of RhoA and RhoA effectors, ROCK1 and ROCK2, in cells related to tissue mineralization: mesenchymal stem cells, chondrocytes, preosteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts...
February 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28184030/genetic-variants-in-rhoa-and-rock1-genes-are-associated-with-the-development-progression-and-prognosis-of-prostate-cancer
#14
Kang Liu, Xiao Li, Jie Wang, Yichun Wang, Huiyu Dong, Jie Li
The contribution of genetic variants in RhoA and ROCK1 genes towards prostate cancer risk has not been reported before. We genotyped six potentially functional genetic variants in a case-control study of 1699 subjects. Overall, we found rs2410 mutant allele and rs2269736 wild allele were risk factors for prostate cancer. Individuals carrying more than two risk alleles were exposed to hazard of prostate cancer. In addition, we demonstrated that the risk of biochemical recurrence might be linked with clinico-pathological characteristics and also genetic factors...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183280/whole-genome-scan-reveals-the-genetic-signature-of-african-ankole-cattle-breed-and-potential-for-higher-quality-beef
#15
Mengistie Taye, Jaemin Kim, Sook Hee Yoon, Wonseok Lee, Olivier Hanotte, Tadelle Dessie, Stephen Kemp, Okeyo Ally Mwai, Kelsey Caetano-Anolles, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods...
February 9, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28131915/rock1-p53-noxa-signaling-mediates-cardiomyocyte-apoptosis-in-response-to-high-glucose-in-vitro-and-vivo
#16
Dongmei Su, Lina Guan, Qianqian Gao, Qian Li, Cuige Shi, Yi Liu, Lei Sun, Cailing Lu, Xu Ma, Jing Zhao
Gestational diabetes mellitus is a risk factor for congenital heart defects; however, the molecular basis of the congenital heart anomalies remains obscure. Previous reports showed a positive correlation between abnormal cardiomyocyte apoptosis and ventricular wall thinness, one type of congenital heart anomaly. This work explored the expression pattern and molecular mechanism of the Rho-associated coiled-coil containing protein kinase 1 (ROCK1) gene in cardiomyocyte apoptosis and genesis of ventricular wall thinness...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28123850/microrna-101-inhibits-proliferation-migration-and-invasion-in-osteosarcoma-cells-by-targeting-rock1
#17
Rui Jiang, Chao Zhang, Guangyao Liu, Rui Gu, Han Wu
Osteosarcoma is a rare malignant bone tumor in adolescents, with high degree of malignancy, and highly incidence of recurrence and metastasis. Our study aimed to explore the role of miR-101 in osteosarcoma cells by targeting ROCK1. In the present study, reverse transcription-quantitative polymerase chain reaction data revealed that miR-101 was down-regulated in the tissue samples of 20 patients with osteosarcoma compared with their matched adjacent non-tumor tissues (P < 0.01). Furthermore, miR-101 was significantly down-regulated in three common OS cell lines, MG63, U2OS, and OS732 compared with the human osteoblast cell line, hFOB1...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28123576/mir-506-suppresses-neuroblastoma-metastasis-by-targeting-rock1
#18
Dianguo Li, Yanhua Cao, Jinliang Li, Jialong Xu, Qian Liu, Xiaogang Sun
Neuroblastoma is a complex form of cancer with highly heterogeneous clinical behavior that arises during childhood from precursor cells of the sympathetic nervous system. In patients with neuroblastoma, mortality often occurs as a result of metastasis. The disease predominantly spreads to bone marrow, with a survival rate of ~40%. The current study demonstrates that microRNA (miR)-506 directly targets and downregulates Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) in transforming growth factor (TGF)-β non-canonical pathways...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28122300/y-27632-a-rho-associated-protein-kinase-inhibitor-inhibits-systemic-lupus-erythematosus
#19
Yuanyuan Wang, Yang Lu, Jixia Chai, Meiqun Sun, Xiaodong Hu, Wenxin He, Min Ge, Changhao Xie
The purpose of the present study was to evaluate whether Rho-kinase inhibition (Y-27632) modulated the expressions of nuclear factor kappaB (NF-κB) in systemic lupus erythematosus. 20 wild type mice and 20 MRL/lpr mice were applied for the research. The animals were randomly assigned to wild type, wild type+Y-27632 group, MRL/lpr group and MRL/lpr+Y-27632 group. 5mg/kg Y-27632 was intravenously injected to inhibit the ROCK expressions.Y-27632 significantly decreased the serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 level in serum of MRL/lpr mice...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28120846/cortactin-deficiency-causes-increased-rhoa-rock1-dependent-actomyosin-contractility-intestinal-epithelial-barrier-dysfunction-and-disproportionately-severe-dss-induced-colitis
#20
A F Citalán-Madrid, H Vargas-Robles, A García-Ponce, M Shibayama, A Betanzos, P Nava, C Salinas-Lara, K Rottner, R Mennigen, M Schnoor
The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin...
January 25, 2017: Mucosal Immunology
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