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Rac1 RhoA

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https://www.readbyqxmd.com/read/29212895/functional-metabolomics-characterizes-a-key-role-for-n-acetyl-neuraminic-acid-in-coronary-artery-diseases
#1
Lei Zhang, Ting-Ting Wei, Yong Li, Jing Li, Yong Fan, Feng-Qing Huang, Yuan-Yuan Cai, Gaoxiang Ma, Jin-Feng Liu, Qian-Qian Chen, Shi-Lei Wang, Honglin Li, Raphael N Alolga, Baolin Liu, Dong-Sheng Zhao, Jian-Hua Shen, Xiang-Ming Wang, Wei Zhu, Ping Li, Lian-Wen Qi
Background -As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. Methods -A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) in the negative ion mode was employed for untargeted analysis of metabolites in plasma...
December 6, 2017: Circulation
https://www.readbyqxmd.com/read/29207169/daam1-activates-rhoa-to-regulate-wnt5a%C3%A2-induced-glioblastoma-cell-invasion
#2
Guiyang Liu, Ting Yan, Xiaorong Li, Jianhui Sun, Bo Zhang, Hongjie Wang, Yichao Zhu
The signaling pathway of dishevelled-associated activator of morphogenesis 1 (Daam1) triggered by Wnt5a drives cell movement and migration during breast cancer metastasis. However, Wnt5a signaling in glioblastoma progression remains poorly defined. Wnt5a expression and activations of RhoA, Cdc42, and Rac1 were detected in human glioblastoma tissues by using ELISA assays and small G-protein activation assays, respectively. The cell invasion rate and Daam1 activation of glioblastoma U251 and T98MG cells were determined by cell invasion assays and pull-down assays, respectively...
December 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29203848/bdnf-release-and-signaling-are-required-for-the-antidepressant-actions-of-glyx-13
#3
T Kato, M V Fogaça, S Deyama, X-Y Li, K Fukumoto, R S Duman
Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29196061/direct-regulation-of-p190rhogef-by-activated-rho-and-rac-gtpases
#4
Olugbenga Dada, Stephen Gutowski, Chad A Brautigam, Zhe Chen, Paul C Sternweis
Rho family GTPases regulate a wide range of cellular processes. This includes cellular dynamics where three subfamilies, Rho, Rac, and Cdc42, are known to regulate cell shape and migration though coordinate action. Activation of Rho proteins largely depends on Rho Guanine nucleotide Exchange Factors (RhoGEFs) through a catalytic Dbl homology (DH) domain linked to a pleckstrin homology (PH) domain that subserves various functions. The PH domains from Lbc RhoGEFs, which specifically activate RhoA, have been shown to bind to activated RhoA...
November 28, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/29172954/ampk-and-autophagy-control-embryonic-elongation-as-part-of-a-rhoa-like-morphogenic-program-in-nematode
#5
Emmanuel Martin, Grégoire Bonnamour, Sarah Jenna
Autophagy is the process where cytosolic components are digested by the cell. This process is required for cell survival in stressful conditions. It was also shown to control cell division and more recently, cell morphology and migration. We characterized signalling pathways enabling embryonic epidermal cells of the nematode Caenorhabditis elegans to elongate along their antero-posterior axis. Previous studies revealed that epidermal cells can adopt either a RhoA-like or a Rac1-like morphogenic program. We show here that the AMP-activated protein kinase (AMPK) and genes controlling autophagy are required for proper elongation of epidermal cells following the RhoA-like program and are dispensable for other cells...
November 25, 2017: Small GTPases
https://www.readbyqxmd.com/read/29172947/crosstalk-between-wip-and-rho-family-gtpases
#6
Inés M Antón, Carla Gómez-Oro, Sergio Rivas, Francisco Wandosell
Through actin-binding proteins such as the neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP-interacting protein (WIP), the Rho family GTPases RhoA, Rac1 and Cdc42 are major modulators of the cytoskeleton. (N-)WASP and WIP control Rho GTPase activity in various cell types, either by direct WIP/(N-)WASP/Cdc42 or potential WIP/RhoA binding, or through secondary links that regulate GTPase distribution and/or transcription levels. WIP helps to regulate filopodium generation and participates in the Rac1-mediated ruffle formation that determines cell motility...
November 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/29155102/targeting-of-rac1-prevents-bronchoconstriction-and-airway-hyperresponsiveness
#7
Gwennan André-Grégoire, Florian Dilasser, Julie Chesné, Faouzi Braza, Antoine Magnan, Gervaise Loirand, Vincent Sauzeau
BACKGROUND: The molecular mechanisms responsible for airway smooth muscle cells (aSMC) contraction and proliferation in airway hyperresponsiveness (AHR) associated with asthma are still largely unknown. The small GTPases of the Rho family (RhoA, Rac1 and Cdc42) play a central role in SMC functions including migration, proliferation and contraction. OBJECTIVE: The objective of this study is to identify the role of Rac1 in aSMC contraction and to investigate its involvement in AHR associated with allergic asthma...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#8
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αMβ2, but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b(-/-) microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47(phox) and superoxide production...
November 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/29133163/non-visual-arrestins-regulate-the-focal-adhesion-formation-via-small-gtpases-rhoa-and-rac1-independently-of-gpcrs
#9
Whitney M Cleghorn, Nada Bulus, Seunghyi Kook, Vsevolod V Gurevich, Roy Zent, Eugenia V Gurevich
Arrestins recruit a variety of signaling proteins to active phosphorylated G protein-coupled receptors in the plasma membrane and to the cytoskeleton. Loss of arrestins leads to decreased cell migration, altered cell shape, and an increase in focal adhesions. Small GTPases of the Rho family are molecular switches that regulate actin cytoskeleton and affect a variety of dynamic cellular functions including cell migration and cell morphology. Here we show that non-visual arrestins differentially regulate RhoA and Rac1 activity to promote cell spreading via actin reorganization, and focal adhesion formation via two distinct mechanisms...
November 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29129556/mechanisms-of-rhoa-inactivation-and-cdc42-and-rac1-activation-during-zebrafish-optic-nerve-regeneration
#10
Toru Matsukawa, Kazune Morita, Shou Omizu, Satoru Kato, Yoshiki Koriyama
When axons of the mammalian central nervous system (CNS) are injured, they fail to regenerate, while those of lower vertebrates undergo regeneration after injury. Wingless-type MMTV integration site family (Wnt) proteins play important roles in the CNS, and are reported to be activated after mammalian spinal cord or brain injury. Moreover, for axon growth to proceed, it is thought that small G-proteins, such as CDC42 and Rac1, need to be activated, whereas RhoA must be inactivated. However, the cell and molecular mechanisms involved in optic nerve regeneration remain unclear...
November 10, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29121646/the-phosphomimetic-mutation-of-syndecan-4-binds-and-inhibits-tiam1-modulating-rac1-activity-in-pdz-interaction-dependent-manner
#11
Aniko Keller-Pinter, Bettina Ughy, Monika Domoki, Aladar Pettko-Szandtner, Tamas Letoha, Jozsef Tovari, Jozsef Timar, Laszlo Szilak
The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan...
2017: PloS One
https://www.readbyqxmd.com/read/29115617/three-dimensional-hydrogel-is-suitable-for-targeted-investigation-of-amoeboid-migration-of-glioma-cells
#12
Yubao Huang, Luqing Tong, Li Yi, Chen Zhang, Long Hai, Tao Li, Shengping Yu, Wei Wang, Zhennan Tao, Haiwen Ma, Peidong Liu, Yang Xie, Xuejun Yang
Glioblastoma (GBM) invasion and migration are key biological behaviors leading to refractoriness to current therapies and infiltration into the non‑tumor brain parenchyma. GBM cell migration is strongly dependent on tumor architecture in vivo, which is absent in traditional two‑dimensional (2D) monolayer culture. The present study applied a three‑dimensional (3D) hydrogel model to rebuild the tumor architecture in vitro. Treatment with NSC23766, a specific inhibitor of Ras‑related C3 botulinum toxin substrate 1 (Rac1), inhibited the mesenchymal invasiveness however triggered the amoeboid motility called mesenchymal‑amoeboid transition (MAT)...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29102373/transcriptomic-analysis-uncovers-novel-synergistic-mechanisms-in-combination-therapy-for-lupus-nephritis
#13
Jia Fu, Zichen Wang, Kyung Lee, Chengguo Wei, Zhengzhao Liu, Mingchao Zhang, Minlin Zhou, Minchao Cai, Weijia Zhang, Peter Y Chuang, Avi Ma'ayan, John Cijiang He, Zhihong Liu
A recent clinical study showed that combination therapy consisting of mycophenolate mofetil, tacrolimus and steroids was shown to be more effective in achieving complete remission in patients with severe forms of lupus nephritis than conventional therapy consisting of intravenous cyclophosphamide and steroids. To explore the underlying molecular and cellular mechanisms of increased efficacy of the combination therapy regimen, we employed a mouse model of lupus nephritis, MRL/lpr mice, and treated them with monotherapies of prednisone, mycophenolate mofetil, or tacrolimus, or with their combination...
November 1, 2017: Kidney International
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#14
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29072354/camp-induced-activation-of-protein-kinase-a-and-p190b-rhogap-mediates-down-regulation-of-tc10-activity-at-the-plasma-membrane-and-neurite-outgrowth
#15
Shingo Koinuma, Kohei Takeuchi, Naoyuki Wada, Takeshi Nakamura
Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP-induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF-treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells...
October 26, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29055784/rac1-modulates-g-protein-coupled-receptor-induced-bronchial-smooth-muscle-contraction
#16
Hiroyasu Sakai, Yuki Kai, Ken Sato, Mitsuo Ikebe, Yohihiko Chiba
Increasing evidence suggests a functional role of RhoA/Rho-kinase signalling as a mechanism for smooth muscle contraction; however, little is known regarding the roles of Rac1 and other members of the Rho protein family. This study aimed to examine whether Rac1 modulates bronchial smooth muscle contraction. Ring preparations of bronchi isolated from rats were suspended in an organ bath, and isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine myosin light chain phosphorylation in bronchial smooth muscle...
October 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29050986/rac1-plays-a-role-in-cxcl12-but-not-ccl3-induced-chemotaxis-and-rac1-gef-inhibitor-nsc23766-has-off-target-effects-on-cxcr4
#17
Shirley C Mills, Lesley Howell, Andrew Beekman, Leanne Stokes, Anja Mueller
Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29043078/a-gap-that-divides
#18
REVIEW
Angika Basant, Michael Glotzer
Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the early Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation in C...
2017: F1000Research
https://www.readbyqxmd.com/read/29042792/low-dose-of-kaempferol-suppresses-the-migration-and-invasion-of-triple-negative-breast-cancer-cells-by-downregulating-the-activities-of-rhoa-and-rac1
#19
Shoushan Li, Ting Yan, Rong Deng, Xuesong Jiang, Huaping Xiong, Yuan Wang, Qiao Yu, Xiaohua Wang, Cheng Chen, Yichao Zhu
PURPOSE: Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. MATERIALS AND METHODS: This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29039527/simvastatin-inhibits-the-expression-of-stemness%C3%A2-related-genes-and-the-metastatic-invasion-of-human-cancer-cells-via-destruction-of-the-cytoskeleton
#20
Rosarita Tatè, Enrica Zona, Rosanna De Cicco, Veronica Trotta, Maria Urciuoli, Alessandro Morelli, Salvatore Baiano, Rosa Carnuccio, Maria Pia Fuggetta, Franco Morelli
Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells...
October 13, 2017: International Journal of Oncology
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