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https://www.readbyqxmd.com/read/28334226/loss-of-cannabinoid-cb-1-receptors-induces-cortical-migration-malformations-and-increases-seizure-susceptibility
#1
Javier Díaz-Alonso, Adán de Salas-Quiroga, Juan Paraíso-Luna, Daniel García-Rincón, Patricia P Garcez, Maddy Parsons, Clara Andradas, Cristina Sánchez, François Guillemot, Manuel Guzmán, Ismael Galve-Roperh
Neuronal migration is a fundamental process of brain development, and its disruption underlies devastating neurodevelopmental disorders. The transcriptional programs governing this process are relatively well characterized. However, how environmental cues instruct neuronal migration remains poorly understood. Here, we demonstrate that the cannabinoid CB 1 receptor is strictly required for appropriate pyramidal neuron migration in the developing cortex. Acute silencing of the CB 1 receptor alters neuronal morphology and impairs radial migration...
October 5, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/28331417/%C3%AE-tocotrienol-inhibits-tgf-%C3%AE-1-induced-contractile-phenotype-expression-of-human-airway-smooth-muscle-cells
#2
Takehito Fukushima, Akira Yamasaki, Tomoya Harada, Hiroki Chikumi, Masanari Watanabe, Ryota Okazaki, Miki Takata, Yasuyuki Hasegawa, Jun Kurai, Masaaki Yanai, Akihiro Yamamoto, Yuriko Sueda, Andrew J Halayko, Eiji Shimizu
BACKGROUND: Tocotrienols, members of the vitamin E family, exist in four different isoforms (α, β, γ and δ tocotrienol) that have can be protective against brain damage, as well as having anticancer effects in vivo and in vitro. We have shown that γ-tocotrienol inhibits human airway smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB by suppressing RhoA activation. In this study, we tested whether γ-tocotrienol modulates transforming growth factor (TGF) -β-induced induction of human airway smooth muscle (ASM) into a contractile phenotype and concomitant synthesis of extracellular matrix proteins...
March 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28330286/effect-of-highly-branched-hyphal-morphology-on-the-enhanced-production-of-cellulase-in-trichoderma-reesei-des-15
#3
Ronglin He, Chen Li, Lijuan Ma, Dongyuan Zhang, Shulin Chen
The morphology of Trichoderma reesei is a vitally important factor for cellulase productivity. This study investigated the effect of hyphal morphology on cellulase production in the hyper-cellulolytic mutant, T. reesei DES-15. With a distinct morphology, T. reesei DES-15 was obtained through Diethyl sulfite (DES) mutagenesis. The hyphal morphology of DES-15 batch-cultured in a 5-L fermentor was significantly shorter and more branched than the parental strain RUT C30. The cellulase production of DES-15 during batch fermentation was 66 % greater than that of RUT C30 when cultured the same conditions...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329735/anti-inflammatory-mechanism-of-ulinastatin-inhibiting-the-hyperpermeability-of-vascular-endothelial-cells-induced-by-tnf-%C3%AE-via-the-rhoa-rock-signal-pathway
#4
Fu Wei, Siyi Liu, Li Luo, Nina Gu, Yan Zeng, Xiaoying Chen, Shan Xu, Dan Zhang
OBJECTIVE: Ulinastatin reduces the high permeability of vascular endothelial cells induced by tumor necrosis factor alpha (TNF-α). This study investigated the molecular mechanism behind this effect, with the aim of understanding the action of ulinastatin in sepsis therapy and exploring novel therapeutic strategies for sepsis patients. METHODS: A TNF-α treated human umbilical vein endothelial cell line (EA.hy926) was employed as an inflammation model. Horseradish peroxidase permeability assays and an epithelial voltmeter method were used to measure the permeability of EA...
March 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28329679/mammalian-diaphanous-1-mediates-a-pathway-for-e-cadherin-to-stabilize-epithelial-barriers-through-junctional-contractility
#5
Bipul R Acharya, Selwin K Wu, Zi Zhao Lieu, Robert G Parton, Stephan W Grill, Alexander D Bershadsky, Guillermo A Gomez, Alpha S Yap
Formins are a diverse class of actin regulators that influence filament dynamics and organization. Several formins have been identified at epithelial adherens junctions, but their functional impact remains incompletely understood. Here, we tested the hypothesis that formins might affect epithelial interactions through junctional contractility. We focused on mDia1, which was recruited to the zonula adherens (ZA) of established Caco-2 monolayers in response to E-cadherin and RhoA. mDia1 was necessary for contractility at the ZA, measured by assays that include a FRET-based sensor that reports molecular-level tension across αE-catenin...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327605/ginsenoside-rb1-protects-against-ischemia-reperfusion-induced-myocardial-injury-via-energy-metabolism-regulation-mediated-by-rhoa-signaling-pathway
#6
Yuan-Chen Cui, Chun-Shui Pan, Li Yan, Lin Li, Bai-He Hu, Xin Chang, Yu-Ying Liu, Jing-Yu Fan, Kai Sun, Quan -Li, Jing-Yan Han
Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28318165/-effects-of-rhoa-silencing-on-proliferation-of-tongue-squamous-cancer-cells
#7
Yan Guoxin, Fan Bing, Zou Ronghai, Zhang Jian, Sun Xiaofeng, Tong Lei, Wang Qimin, Han Jinhong, Lu Xufei, Wang Ying, Zhou Yuan, He Zongxuan, Liao Yixiang, Li Ning, Cao Lei, Chen Zhenggang
OBJECTIVE: This study investigated the effect of RhoA silencing through RNA interference on proliferation and growth of tongue cancer cells, as well as explored the possible mechanisms of this effect. METHODS: SSC-4 tongue cancer cells were cultured in vitro and then transfected with small interfering RNA to knock down RhoA expression. The tested cells were divided into three groups: experimental group (experimental group 1: transfected with RhoA-siRNA-1; experi-mental group 2: transfected with RhoA-siRNA-2), negative control group (transfected by random sequence NC-siRNA), and blank control group (transfected with Lipofectamine)...
December 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#8
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/28303627/camp-dependent-regulation-of-rhoa-rho-kinase-attenuates-detrusor-overactivity-in-a-novel-mouse-experimental-model
#9
William Akakpo, Biljana Musicki, Arthur L Burnett
OBJECTIVES: To investigate detrusor function and cAMP activation as a possible target for detrusor overactivity in an experimental model lacking a key denitrosylation enzyme, S-nitrosoglutathione reductase (GSNOR). MATERIALS AND METHODS: GSNOR-deficient (GSNOR(-/-) ) (n=30) and wild-type (WT) mice (n=26) were treated for 7 days with the cAMP activator, colforsin (1mg/kg), or vehicle intraperitoneally. Cystometric studies or molecular analyses of bladder specimens were performed...
March 16, 2017: BJU International
https://www.readbyqxmd.com/read/28303576/nonmuscle-nm-myosin-heavy-chain-phosphorylation-regulates-the-formation-of-nm-myosin-filaments-adhesome-assembly-and-smooth-muscle-contraction
#10
Wenwu Zhang, Susan J Gunst
The molecular function of nonmuscle (NM) isoforms of myosin II in smooth muscle (SM) tissues, and their possible role in contraction are largely unknown. We evaluated the function of NM myosin during contractile stimulation of canine tracheal SM tissues. Stimulation with ACh caused NM myosin filament assembly, as assessed by a Triton solubility assay and a proximity ligation assay to measure interactions between NM myosin monomers. ACh stimulated the phosphorylation of NM myosin heavy chain (HC) on Ser1943 in tracheal SM tissues, which can regulate NM myosin IIA filament assembly in vitro...
March 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28301477/fragility-of-foot-process-morphology-in-kidney-podocytes-arises-from-chaotic-spatial-propagation-of-cytoskeletal-instability
#11
Cibele V Falkenberg, Evren U Azeloglu, Mark Stothers, Thomas J Deerinck, Yibang Chen, John C He, Mark H Ellisman, James C Hone, Ravi Iyengar, Leslie M Loew
Kidney podocytes' function depends on finger-like projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology...
March 16, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28301299/differential-role-for-pak1-and-pak4-during-the-invadopodia-lifecycle
#12
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Claire M Wells
PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZRho-GEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics...
March 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28300846/regulation-of-rhoa-activity-by-the-cellular-prion-protein
#13
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/28300720/effect-of-hydrogel-elasticity-and-ephrinb2-immobilized-manner-on-runx2-expression-of-human-mesenchymal-stem-cells
#14
Hiroyuki Toda, Masaya Yamamoto, Hiroshi Uyama, Yasuhiko Tabata
The objective of this study is to design the manner of ephrinB2 immobilized onto polyacrylamide (PAAm) hydrogels with varied elasticity and evaluate the effect of hydrogels elasticity and the immobilized manner of ephrinB2 on the Runx2 expression of human mesenchymal stem cells (hMSC). The PAAm hydrogels were prepared by the radical polymerization of acrylamide (AAm), and N,N'-methylenebisacrylamide (BIS). By changing the BIS concentration, the elasticity of PAAm hydrogels changed from 1 to 70 kPa. For the bio-specific immobilization of ephrinB2, a chimeric protein of ephrinB2 and Fc domain was immobilized onto protein A-conjugated PAAm hydrogels by making use of the bio-specific interaction between the Fc domain and protein A...
March 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28300193/interplay-of-myosin-phosphatase-and-protein-phosphatase-2a-in-the-regulation-of-endothelial-nitric-oxide-synthase-phosphorylation-and-nitric-oxide-production
#15
Róbert Bátori, Bálint Bécsi, Dénes Nagy, Zoltán Kónya, Csaba Hegedűs, Zsuzsanna Bordán, Alexander Verin, Beáta Lontay, Ferenc Erdődi
The inhibitory phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) at Thr497 (eNOS(pThr497)) by protein kinase C or RhoA-activated kinase is a major regulatory determinant of eNOS activity. The signalling mechanisms involved in the dephosphorylation of eNOS(pThr497) have not yet been clarified. This study identifies myosin phosphatase (MP) holoenzyme consisting of protein phosphatase-1 catalytic subunit (PP1c) and MP target subunit-1 (MYPT1) as an eNOS(pThr497) phosphatase. In support of this finding are: (i) eNOS and MYPT1 interacts in various endothelial cells (ECs) and in in vitro binding assays (ii) MYPT1 targets and stimulates PP1c toward eNOS(pThr497) substrate (iii) phosphorylation of MYPT1 at Thr696 (MYPT1(pThr696)) controls the activity of MP on eNOS(pThr497)...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289332/pi3k%C3%AE-isoform-dependent-activation-of-rhoa-regulates-wnt5a-induced-osteosarcoma-cell-migration
#16
Ailiang Zhang, Ting Yan, Kun Wang, Zhihui Huang, Jinbo Liu
BACKGROUND: We have reported that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway mediated Wnt5a-induced osteosarcoma cell migration. However, the signaling pathways regulating Wnt5a/PI3K/Akt-mediated cell migration remains poorly defined in osteosarcoma cells. METHODS: We evaluated the activations of RhoA, Rac1 and Cdc42 in osteosarcoma MG-63 and U2OS cells with small G-protein activation assay. Boyden chamber assays were used to confirm the migration of cells transfected indicated constructs or siRNA specific against RhoA...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28287334/regulation-of-rho-gtpase-activity-at-the-leading-edge-of-migrating-cells-by-p190rhogap
#17
Aurélien Bidaud-Meynard, Fabien Binamé, Valérie Lagrée, Violaine Moreau
Cell migration, a key feature of embryonic development, immunity, angiogenesis, and tumor metastasis, is based on the coordinated regulation of actin dynamics and integrin-mediated adhesion. Rho GTPases play a major role in this phenomenon by regulating the onset and maintenance of actin-based protruding structures at cell leading edges (i.e. lamellipodia and filopodia) and contractile structures (i.e., stress fibers) at their trailing edge. While spatio-temporal analysis demonstrated the tight regulation of Rho GTPases at the migration front during cell locomotion, little is known about how the main regulators of Rho GTPase activity, such as GAPs, GEFs and GDIs, play a role in this process...
March 13, 2017: Small GTPases
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#18
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28284839/depletion-of-tumor-suppressor-kank1-induces-centrosomal-amplification-via-hyperactivation-of-rhoa
#19
Jun-Ichiro Suzuki, Badal Chandra Roy, Takunori Ogaeri, Naoto Kakinuma, Ryoiti Kiyama
Chromosome instability, frequently found in cancer cells, is caused by a deficiency in cell division, including centrosomal amplification and cytokinesis failure, and can result in abnormal chromosome content or aneuploidy. The small GTPase pathways have been implicated as important processes in cell division. We found that knockdown of a tumor suppressor protein Kank1 increases the number of cells with a micronucleus or bi-/multi-nuclei, which was likely caused by centrosomal amplification. Kank1 interacts with Daam1, known to bind to and activate a small GTPase, RhoA, in actin assembly...
March 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28283529/targeting-the-rhoa-rock-pathway-to-reverse-t-cell-dysfunction-in-sle
#20
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
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