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https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#1
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#2
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#3
Mamiko Sakata-Yanagimoto, Rie Nakamoto-Matsubara, Daisuke Komori, Tran B Nguyen, Keiichiro Hattori, Toru Nanmoku, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa, Atsushi Shinagawa, Shigeru Chiba
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis...
June 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28630165/the-cell-adhesion-molecule-chl1-interacts-with-patched-1-to-regulate-apoptosis-during-postnatal-cerebellar-development
#4
Jelena Katic, Gabriele Loers, Jelena Tosic, Melitta Schachner, Ralf Kleene
The immunoglobulin superfamily adhesion molecule close homolog of L1 (CHL1) plays important roles during nervous system development. Here, we identified the hedgehog receptor patched-1 (PTCH1) as novel CHL1 binding partner and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Co-localization and -immunoprecipitation of CHL1 with PTCH1 suggest an association of CHL1 with this major component of the hedgehog signaling pathway. The trans-interaction of CHL1 with PTCH1 promotes neuronal survival in cultures of dissociated cerebellar granule cells and of organotypic cerebellar slices...
June 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28630045/structure-based-analysis-of-the-guanine-nucleotide-exchange-factor-smggds-reveals-armadillo-repeat-motifs-and-key-regions-for-activity-and-gtpase-binding
#5
Hikaru Shimizu, Sachiko Toma-Fukai, Shinya Saijo, Nobutaka Shimizu, Kenji Kontani, Toshiaki Katada, Toshiyuki Shimizu
Small GTPases are molecular switches that have critical biological roles and are controlled by GTPase-activating proteins and guanine-nucleotide exchange factors (GEFs). The smg GDP dissociation stimulator (SmgGDS) protein functions as a GEF for the RhoA and RhoC small GTPases. SmgGDS has various regulatory roles, including small GTPase trafficking and localization and as a molecular chaperone, and interacts with many small GTPases possessing polybasic regions. Two SmgGDS splice variants, SmgGDS-558 and SmgGDS-607, differ in GEF activity and binding affinity for RhoA depending on the lipidation state, but the reasons for these differences are unclear...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28626446/gnrh-induces-erk-dependent-bleb-formation-in-gonadotrope-cells-involving-recruitment-of-members-of-a-gnrh-receptor-associated-signalosome-to-the-blebs
#6
Liat Rahamim-Ben Navi, Anna Tsukerman, Alona Feldman, Philippa Melamed, Melanija Tomić, Stanko S Stojilkovic, Ulrich Boehm, Rony Seger, Zvi Naor
We have previously described a signaling complex (signalosome) associated with the GnRH receptor (GnRHR). We now report that GnRH induces bleb formation in the gonadotrope-derived LβT2 cells. The blebs appear within ~2 min at a turnover rate of ~2-3 blebs/min and last for at least 90 min. Formation of the blebs requires active ERK1/2 and RhoA-ROCK but not active c-Src. Although the following ligands stimulate ERK1/2 in LβT2 cells: EGF > GnRH > PMA > cyclic adenosine monophosphate (cAMP), they produced little or no effect on bleb formation as compared to the robust effect of GnRH (GnRH > PMA > cAMP > EGF), indicating that ERK1/2 is required but not sufficient for bleb formation possibly due to compartmentalization...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28624843/expressions-of-ras-homolog-gene-family-member-a-rhoa-and-cyclooxygenase-2-cox-2-proteins-in-early-gastric-cancer-and-their-role-in-the-development-of-gastric-cancer
#7
Li Song, Yali Guo, Baohong Xu
BACKGROUND This research focused on detecting the expressions of RhoA and cyclooxygenase-2 (COX-2) proteins in early gastric cancer tissues and to explore their role in the development of gastric cancer. MATERIAL AND METHODS Surgically resected gastric cancer tissues and the paired normal paracancerous tissues were collected from 26 patients with early gastric cancer from January 2015 to November 2015. The expressions of RhoA and COX-2 proteins were detected by using RT-PCR and immunohistochemistry techniques, respectively...
June 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28621452/osteogenic-commitment-and-differentiation-of-human-mesenchymal-stem-cells-by-low-intensity-pulsed-ultrasound-stimulation
#8
Viviana Costa, Valeria Carina, Simona Fontana, Angela De Luca, Francesca Monteleone, Stefania Pagani, Maria Sartori, Stefania Setti, Cesare Faldini, Riccardo Alessandro, Milena Fini, Gianluca Giavaresi
Low-intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm(2) LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7d, 14d, 21d). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis...
June 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28619708/arhgap18-downregulation-by-mir-200b-suppresses-metastasis-of-triple-negative-breast-cancer-by-enhancing-activation-of-rhoa
#9
Brock Humphries, Zhishan Wang, Yunfei Li, Jing-Ru Jhan, Yiguo Jiang, Chengfeng Yang
Rho GTPases activated in cancer cells drive proliferation, migration and metastasis. Thus, RhoGAP proteins which negatively regulate Rho GTPases are generally thought to function as tumor suppressors. Here this expectation was challenged by characterization of ARHGAP18, a RhoGAP family member that is selectively overexpressed in highly migratory triple negative breast cancer (TNBC) cells. In human breast tumors, higher ARHGAP18 levels associated with worse overall survival, recurrence-free survival and metastasis-free survival...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28614361/molecular-cloning-characterization-and-expression-analysis-of-frizzled-6-in-the-small-intestine-of-pigs-sus-scrofa
#10
Lijun Zou, Xiaocheng Wang, Liping Jiang, Shengping Wang, Xia Xiong, Huansheng Yang, Wei Gao, Min Gong, Chien-An A Hu, Yulong Yin
Frizzled 6 (FZD6) encodes an integral membrane protein that functions in multiple signal transduction pathways, for example, as a receptor in Wnt/planar cell polarity (PCP) signaling pathway for polarized cell migration and organ morphogenesis. Mutations in FZD6 have been identified in a variety of tumors. In this study, the full-length cDNA of Sus scrofa FZD6 (Sfz6) was cloned and characterized. Nucleotide sequence analysis demonstrates that the Sfz6 gene encodes the 712 amino-acid (aa) protein with seven transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28608941/tgf-%C3%AE-stimulates-expression-of-chondroitin-polymerizing-factor-in-nucleus-pulposus-cells-through-the-smad3-rhoa-rock1-and-mapk-signaling-pathways
#11
Bo Hu, Chen Xu, Peng Cao, Ye Tian, Ying Zhang, Changgui Shi, Jun Xu, Wen Yuan, Huajiang Chen
The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF-β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF-β induced ChPF expression and enhanced Smad2/3, RhoA/ ROCK activation, and the JNK, p38 and ERK1/2 MAPK signaling pathways...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28608226/blocking-rhoa-rock-inhibits-the-pathogenesis-of-pemphigus-vulgaris-by-suppressing-oxidative-stress-and-apoptosis-through-tak1-nod2-mediated-nf-%C3%AE%C2%BAb-pathway
#12
Junqin Liang, Xuewen Zeng, Yilinuer Halifu, Wenjing Chen, Fengxia Hu, Peng Wang, Huan Zhang, Xiaojing Kang
Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein...
June 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28604737/optogenetic-control-of-rhoa-reveals-zyxin-mediated-elasticity-of-stress-fibres
#13
Patrick W Oakes, Elizabeth Wagner, Christoph A Brand, Dimitri Probst, Marco Linke, Ulrich S Schwarz, Michael Glotzer, Margaret L Gardel
Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28600494/serum-lipid-levels-and-risk-of-hand-osteoarthritis-the-chingford-prospective-cohort-study
#14
M Garcia-Gil, C Reyes, R Ramos, M T Sanchez-Santos, D Prieto-Alhambra, T D Spector, D J Hart, N K Arden
The development of hand osteoarthritis (HOA) could be linked to hyperlipidaemia. No longitudinal studies have addressed the relationship between serum lipid profile and HOA. The study aim was to determine the association between serum lipid profile and the incidence of radiographic hand osteoarthritis (RHOA). All women in a prospective population-based cohort from the Chingford study with available baseline lipid measurements and without RHOA on a baseline were included. Study outcome was the incidence of RHOA in year 11 of follow-up...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599441/effects-of-silencing-endothelin-1-on-invasion-and-vascular-formation-in-lung-cancer
#15
Zhen-Yu Zhang, Li-Li Chen, Wei Xu, Keshavraj Sigdel, Xing-Tang Jiang
Endothelin-1 (ET-1), which exists not only in the vascular endothelium but is also widely present in various tissues and cells, is an important cardiovascular regulatory factor that serves an important role in maintaining the basal vascular tone and homeostasis in the cardiovascular system. In the present study, the ET-1 gene was silenced by RNA interference, and the effects on lung cancer cell proliferation and tumor cell invasion were then detected by Cell Counting kit-8 and Transwell assays. In addition, the expression of apoptosis, growth and invasion-associated proteins, including RhoA/C, vascular endothelial growth factor, pigment epithelium-derived factor, AKT, E-cadherin and cyclooxygenase-2 was evaluated by western blotting upon silencing ET-1...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28589995/trans-polydatin-protects-the-mouse-heart-against-ischemia-reperfusion-injury-via-inhibition-of-the-renin-angiotensin-system-ras-and-rho-kinase-rock-activity
#16
Dong Ming, Liao Songyan, Chen Yawen, Zheng Na, Ma Jing, Xiao Zhaowen, Liu Ye, Ding Wa, Liu Jie
BACKGROUND: Recent studies highlighted the protective benefits of a Chinese herb extract from polygonum cuspidatum, trans-polydatin, on cardiac disease. We investigated the therapeutic effect of trans-polydatin on myocardial ischemia/reperfusion (IR) injury and the underlying mechanisms related to the renin-angiotensin system (RAS) and RhoA kinase (ROCK) pathway. METHODS AND RESULTS: Experiments were performed on neonatal rats' ventricular myocytes that were subjected to hypoxia-reoxygenation (simulated IR, SIR) and on adult mice which were subjected to left anterior descending coronary artery occlusion for 45 min followed by a one-week reperfusion...
June 7, 2017: Food & Function
https://www.readbyqxmd.com/read/28586283/mkl1-dependent-gene-activation-is-sufficient-to-induce-actin-cap-assembly
#17
Ketan Thakar, Christopher W Carroll
Actin-dependent forces mechanically control both the position and shape of the nucleus. While the mechanisms that establish nuclear position are well defined, less understood is how actin filaments determine nuclear shape. We recently showed that nuclear envelope-spanning LINC complexes promote stress fiber assembly by activating the small GTPase RhoA and Mkl1-dependent gene activation. We now report that a subset of these stress fibers associate with the apical face of the nuclear envelope through LINC complexes that contain the inner nuclear membrane protein Sun2...
June 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28585695/the-rhogap-myo9b-promotes-bone-growth-by-mediating-osteoblastic-responsiveness-to-igf-1
#18
Brooke K McMichael, Yong-Hoon Jeong, Justin A Auerbach, Cheol-Min Han, Ryan Sedlar, Vikram Shettigar, Martin Bähler, Sudha Agarwal, Do-Gyoon Kim, Beth S Lee
The RhoA subfamily of Rho GTPases regulates actin-based cellular functions in bone such as differentiation, migration, and mechanotransduction. Polymorphisms or genetic ablation of RHOA and some of its regulatory guanine exchange factors (GEFs) have been linked to poor bone health in humans and mice, but the effects of RhoA-specific GTPase-activating proteins (GAPs) on bone quality have not yet been identified. Therefore, we examined the consequences of RhoGAP Myo9b gene knockout on bone growth, phenotype and cellular activity...
June 6, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28584231/identification-of-15-novel-risk-loci-for-coronary-artery-disease-and-genetic-risk-of-recurrent-events-atrial-fibrillation-and-heart-failure
#19
Niek Verweij, Ruben N Eppinga, Yanick Hagemeijer, Pim van der Harst
Coronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic variants passing P <× 10(-5) in CARDIoGRAMplusC4D with novel data made available by UK Biobank. Of the 161 genetic variants studied, 71 reached genome wide significance (p < 5 × 10(-8)) including 15 novel loci. These novel loci include multiple genes that are involved in angiogenesis (TGFB1, ITGB5, CDH13 and RHOA) and 2 independent variants in the TGFB1 locus...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28584191/arhgap42-is-activated-by-src-mediated-tyrosine-phosphorylation-to-promote-cell-motility
#20
Weifeng Luo, Radoslav Janoštiak, Ondřej Tolde, Larisa M Ryzhova, Lenka Koudelková, Michal Dibus, Jan Brábek, Steven K Hanks, Daniel Rosel
The tyrosine kinase Src acts as a key regulator of cell motility by phosphorylating multiple protein substrates that control cytoskeletal and adhesion dynamics. In an earlier phosphotyrosine proteomics study we identified a novel Rho‑GTPase activating protein, now called ARHGAP42, as a likely biologically relevant Src substrate. ARHGAP42 is a member of a family of RhoGAPs distinguished by tandem BAR‑PH domains lying N‑terminal to the GAP domain. Like other family members, ARHGAP42 acts preferentially as a GAP for RhoA...
June 5, 2017: Journal of Cell Science
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