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https://www.readbyqxmd.com/read/28225457/rhoa-rock-pathway-inhibition-by-fasudil-suppresses-the-vasculogenic-mimicry-of-u2os-osteosarcoma-cells-in-vitro
#1
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/28223230/myotoxicity-of-statins-mechanism-of-action
#2
REVIEW
Patrick du Souich, Ghislaine Roederer, Robert Dufour
Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations of statins in the myocyte and/or in presence of muscular conditions that may predispose to SIM. High concentrations of statins in the myocyte may occur whenever the activity of liver influx membrane transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular efflux transporters, MDR1 and BCRP, is reduced...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222172/rhoa-promotes-epidermal-stem-cell-proliferation-via-pkn1-cyclin-d1-signaling
#3
Fan Wang, Rixing Zhan, Liang Chen, Xia Dai, Wenping Wang, Rui Guo, Xiaoge Li, Zhe Li, Liang Wang, Shupeng Huang, Jie Shen, Shirong Li, Chuan Cao
OBJECTIVE: Epidermal stem cells (ESCs) play a critical role in wound healing, but the mechanism underlying ESC proliferation is not well defined. Here, we explore the effects of RhoA on ESC proliferation and the possible underlying mechanism. METHODS: Human ESCs were enriched by rapid adhesion to collagen IV. RhoA(+/+)(G14V), RhoA(-/-)(T19N) and pGFP control plasmids were transfected into human ESCs. The effect of RhoA on cell proliferation was detected by cell proliferation and DNA synthesis assays...
2017: PloS One
https://www.readbyqxmd.com/read/28222099/morphological-study-of-tooth-development-in-podoplanin-deficient-mice
#4
Kenyo Takara, Naoki Maruo, Kyoko Oka, Chiaki Kaji, Yuji Hatakeyama, Naruhiko Sawa, Yukinari Kato, Junro Yamashita, Hiroshi Kojima, Yoshihiko Sawa
Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28220837/a-novel-role-of-the-organizer-gene-goosecoid-as-an-inhibitor-of-wnt-pcp-mediated-convergent-extension-in-xenopus-and-mouse
#5
Bärbel Ulmer, Melanie Tingler, Sabrina Kurz, Markus Maerker, Philipp Andre, Dina Mönch, Marina Campione, Kirsten Deißler, Mark Lewandoski, Thomas Thumberger, Axel Schweickert, Abraham Fainsod, Herbert Steinbeißer, Martin Blum
Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216049/chronic-treatment-with-fluoxetine-modulates-vascular-adrenergic-responses-by-inhibition-of-pre-and-post-synaptic-mechanisms
#6
Camila A Pereira, Fernanda L Rodrigues, Silvia G Ruginsk, Camila Z Zanotto, José A Rodrigues, Diego A Duarte, Claudio M Costa-Neto, Leonardo B Resstel, Fernando S Carneiro, Rita C Tostes
Fluoxetine, a serotonin reuptake inhibitor (SSRI), has other effects in addition to blocking serotonin reuptake, including changes in the vasomotor tone. Whereas many studies focused on the acute effects of fluoxetine in the vasculature, its chronic effects are still limited. In the present study, we tested the hypothesis that chronic fluoxetine treatment modulates adrenergic vascular responses by interfering with post- and pre-synaptic mechanisms. Wistar rats were treated with vehicle (water) or chronic fluoxetine (10mg/kg/day) for 21 days...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28214845/simulated-microgravity-promotes-angiogenesis-through-rhoa-dependent-rearrangement-of-the-actin-cytoskeleton
#7
Fei Shi, Yong-Chun Wang, Ze-Bing Hu, Hong-Yu Xu, Jing Sun, Yuan Gao, Xiao-Tao Li, Chang-Bin Yang, Chao Xie, Cheng-Fei Li, Shu Zhang, Jiang-Dong Zhao, Xin-Sheng Cao, Xi-Qing Sun
BACKGROUND/AIMS: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. METHODS: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity...
January 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#8
REVIEW
Ana María López-Colomé, Irene Lee-Rivera, Regina Benavides-Hidalgo, Edith López
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms...
February 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#9
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28213288/inhibition-of-estrogen-related-receptor-%C3%AE-attenuates-vascular-smooth-muscle-cell-proliferation-and-migration-by-regulating-rhoa-p27-kip1-and-%C3%AE-catenin-wnt4-signaling-pathway
#10
Qunyi Li, Lei Zhu, Liudi Zhang, Haifei Chen, Yingfeng Zhu, Yongli Du, Wanxian Zhong, Mingkang Zhong, Xiaojin Shi
RhoA/p27(Kip1) and β-Catenin/Wnt4 signaling processes play central roles in proliferation and migration in vascular smooth muscle cells (VSMCs). ERRα, a member of orphan nuclear receptors, is a potent prognostic factor in breast, ovarian, colon and other types of tumors. However, biological significance of ERRα in VSMCs as well as the molecular mechanisms remains largely unknown. Therefore, the present study was designed to investigate whether ERRα is involved in the proliferation and migration of VSMCs in vitro and neointimal formation in vivo...
February 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28212799/rho-mancing-to-sensitize-calcium-signaling-for-contraction-in-the-vasculature-role-of-rho-kinase
#11
T Szasz, R C Webb
Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28199362/flowtaxis-of-osteoblast-migration-under-fluid-shear-and-the-effect-of-rhoa-kinase-silencing
#12
Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Il Keun Kwon, Jung Yul Lim
Despite the important role of mechanical signals in bone remodeling, relatively little is known about how fluid shear affects osteoblastic cell migration behavior. Here we demonstrated that MC3T3-E1 osteoblast migration could be activated by physiologically-relevant levels of fluid shear in a shear stress-dependent manner. Interestingly, shear-sensitive osteoblast migration behavior was prominent only during the initial period after the onset of the steady flow (for about 30 min), exhibiting shear stress-dependent migration speed, displacement, arrest coefficient, and motility coefficient...
2017: PloS One
https://www.readbyqxmd.com/read/28197417/basal-and-activated-calcium-sensitization-mediated-by-rhoa-rho-kinase-pathway-in-rats-with-genetic-and-salt-hypertension
#13
Michal Behuliak, Michal Bencze, Ivana Vaněčková, Jaroslav Kuneš, Josef Zicha
Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28196833/characterization-of-the-activation-of-small-gtpases-by-their-gefs-on-membranes-using-artificial-membrane-tethering
#14
François Peurois, Simon Veyron, Yann Ferrandez, Ilham Ladid, Sarah Benabdi, Mahel Zeghouf, Gérald Peyroche, Jacqueline Cherfils
Attachment of active, GTP-bound small GTPases to membranes by post-translational lipid modifications is pivotal for their ability to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by GEFs and their termination by GAPs. Here we replaced the lipid modification by a histidine tag in eleven full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid containing membranes and characterize the kinetics of their activation by GEFs...
February 14, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28196303/the-long-noncoding-rna-schlah-suppresses-metastasis-of-hepatocellular-carcinoma-through-interacting-with-fus
#15
Zhouhong Ge, Zhuoan Cheng, Xinrong Yang, Xisong Huo, Ning Wang, Hui Wang, Cun Wang, Dishui Gu, Fangyu Zhao, Ming Yao, Jia Fan, Wenxin Qin
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells...
February 14, 2017: Cancer Science
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
#16
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, pre-osteoblasts, osteoblasts, osteocytes, lining cells and osteoclasts...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28186127/optogenetic-control-of-cellular-forces-and-mechanotransduction
#17
Léo Valon, Ariadna Marín-Llauradó, Thomas Wyatt, Guillaume Charras, Xavier Trepat
Contractile forces are the end effectors of cell migration, division, morphogenesis, wound healing and cancer invasion. Here we report optogenetic tools to upregulate and downregulate such forces with high spatiotemporal accuracy. The technology relies on controlling the subcellular activation of RhoA using the CRY2/CIBN light-gated dimerizer system. We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or to the mitochondrial membrane...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28184941/combined-effects-of-furanodiene-and-doxorubicin-on-the-migration-and-invasion-of-mda-mb-231-breast-cancer-cells-in-vitro
#18
Zhang-Feng Zhong, Wen Tan, Ke Tian, Hua Yu, Wen-An Qiang, Yi-Tao Wang
Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells...
February 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28184030/genetic-variants-in-rhoa-and-rock1-genes-are-associated-with-the-development-progression-and-prognosis-of-prostate-cancer
#19
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/28183205/inhibition-of-rho-kinase-protects-from-ischaemia-reperfusion-injury-via-regulation-of-arginase-activity-and-nitric-oxide-synthase-in-type-1-diabetes
#20
Yahor Tratsiakovich, Attila Kiss, Adrian T Gonon, Jiangning Yang, Per-Ove Sjöquist, John Pernow
AIM: RhoA/Rho-associated kinase and arginase are implicated in vascular complications in diabetes. This study investigated whether RhoA/Rho-associated kinase and arginase inhibition protect from myocardial ischaemia-reperfusion injury in type 1 diabetes and the mechanisms behind these effects. METHODS: Rats with streptozotocin-induced type 1 diabetes and non-diabetic rats were subjected to 30 min myocardial ischaemia and 2 h reperfusion after being randomized to treatment with (1) saline, (2) RhoA/Rho-associated kinase inhibitor hydroxyfasudil, (3) nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate followed by hydroxyfasudil, (4) arginase inhibitor N-omega-hydroxy-nor-l-arginine, (5) N(G)-monomethyl-l-arginine monoacetate followed by N-omega-hydroxy-nor-l-arginine or (6) N(G)-monomethyl-l-arginine monoacetate given intravenous before ischaemia...
February 1, 2017: Diabetes & Vascular Disease Research
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