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https://www.readbyqxmd.com/read/29155102/targeting-of-rac1-prevents-bronchoconstriction-and-airway-hyperresponsiveness
#1
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
#2
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/29152087/specific-role-of-rhoc-in-tumor-invasion-and-metastasis
#3
Sarah Lang, Hauke Busch, Melanie Boerries, Tilman Brummer, Sylvia Timme, Silke Lassmann, Klaus Aktories, Gudula Schmidt
Rho GTPases are regulators of many cellular functions and are often dysregulated in cancer. However, the precise role of Rho proteins for tumor development is not well understood. In breast cancer, overexpression of RhoC is linked with poor prognosis. Here, we aim to compare the function of RhoC and its homolog family member RhoA in breast cancer progression. We established stable breast epithelial cell lines with inducible expression of RhoA and RhoC, respectively. Moreover, we made use of Rho-activating bacterial toxins (Cytotoxic Necrotizing Factors) to stimulate the endogenous pool of Rho GTPases in benign breast epithelial cells and simultaneously knocked down specific Rho proteins...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149906/forebrain-specific-conditional-silencing-of-staufen2-alters-synaptic-plasticity-learning-and-memory-in-rats
#4
Stefan M Berger, Iván Fernández-Lamo, Kai Schönig, Sandra M Fernández Moya, Janina Ehses, Rico Schieweck, Stefano Clementi, Thomas Enkel, Sascha Grothe, Oliver von Bohlen Und Halbach, Inmaculada Segura, José María Delgado-García, Agnès Gruart, Michael A Kiebler, Dusan Bartsch
BACKGROUND: Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo. RESULTS: To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons...
November 17, 2017: Genome Biology
https://www.readbyqxmd.com/read/29148036/function-and-mechanism-of-the-pyrin-inflammasome
#5
REVIEW
Rosalie Heilig, Petr Broz
Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as Familial Mediterranean Fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Recent insights have now revealed how pyrin is activated during infection, providing a molecular basis for the understanding of such disease-causing mutations in pyrin...
November 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29146911/cytokinesis-requires-localized-%C3%AE-actin-filament-production-by-an-actin-isoform-specific-nucleator
#6
A Chen, P D Arora, C A McCulloch, A Wilde
Cytokinesis is initiated by the localized assembly of the contractile ring, a dynamic actomyosin structure that generates a membrane furrow between the segregating chromosomal masses to divide a cell into two. Here we show that the stabilization and organization of the cytokinetic furrow is specifically dependent on localized β-actin filament assembly at the site of cytokinesis. β-actin filaments are assembled directly at the furrow by an anillin-dependent pathway that enhances RhoA-dependent activation of the formin DIAPH3, an actin nucleator...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146177/clostridium-difficile-and-clostridium-sordellii-toxins-proinflammatory-versus-anti-inflammatory-response
#7
Michel R Popoff
Clostridium difficile and Clostridium sordellii produce related potent toxins (C. difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and hemorrhagic toxin (TcsH)) which belong to the large clostridial glucosylating toxin (LCGT) family. TcsL is the main C. sordellii toxin as most of toxigenic C. sordellii strains only synthesize this toxin. Intestinal colonization by C. difficile subsequently to unbalanced microbiota is accompanied by release of toxins which induce local tissue destruction and severe inflammatory response...
November 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29142175/macrophage-differentiation-induced-by-pma-is-mediated-by-activation-of-rhoa-rock-signaling
#8
Lifeng Yang, Fan Dai, Lian Tang, Yulan Le, Wenjuan Yao
In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29137281/hic-5-regulates-epithelial-to-mesenchymal-transition-in-ovarian-cancer-cells-in-a-tgf%C3%AE-1-independent-manner
#9
Razan Sheta, Zhi-Qiang Wang, Magdalena Bachvarova, Marie Plante, Jean Gregoire, Marie-Claude Renaud, Alexandra Sebastianelli, Stephane Gobeil, Chantale Morin, Elizabeth Macdonald, Barbara Vanderhyden, Dimcho Bachvarov
The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-β-induced epithelial-to-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#10
Dounia Abbadi, Fanny Laroumanie, Mathilde Bizou, Joffrey Pozzo, Danièle Daviaud, Christine Delage, Denis Calise, Fréderique Gaits-Iacovoni, Marianne Dutaur, Florence Tortosa, Edith Renaud-Gabardos, Victorine Douin-Echinard, Anne-Catherine Prats, Jerome Roncalli, Angelo Parini, Nathalie Pizzinat
Aims: Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results: We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells...
November 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29133163/non-visual-arrestins-regulate-the-focal-adhesion-formation-via-small-gtpases-rhoa-and-rac1-independently-of-gpcrs
#11
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/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#12
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29130930/leukocyte-rhoa-exchange-factor-arhgef1-mediates-vascular-inflammation-and-atherosclerosis
#13
Maria Luigia Carbone, Gilliane Chadeuf, Sandrine Heurtebise-Chrétien, Xavier Prieur, Thibault Quillard, Yann Goueffic, Nathalie Vaillant, Marc Rio, Laure Castan, Maxim Durand, Céline Baron-Menguy, Julien Aureille, Juliette Desfrançois, Angela Tesse, Raul M Torres, Gervaise Loirand
Abnormal activity of the renin-angiotensin-aldosterone system plays a causal role in the development of hypertension, atherosclerosis, and associated cardiovascular events such as myocardial infarction, stroke, and heart failure. As both a vasoconstrictor and a proinflammatory mediator, angiotensin II (Ang II) is considered a potential link between hypertension and atherosclerosis. However, a role for Ang II-induced inflammation in atherosclerosis has not been clearly established, and the molecular mechanisms and intracellular signaling pathways involved are not known...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29129684/rhoa-gtpase-controls-yap-mediated-ereg-signaling-in-small-intestinal-stem-cell-maintenance
#14
Ming Liu, Zheng Zhang, Leesa Sampson, Xuan Zhou, Kodandaramireddy Nalapareddy, Yuxin Feng, Shailaja Akunuru, Jaime Melendez, Ashley Kuenzi Davis, Feng Bi, Hartmut Geiger, Mei Xin, Yi Zheng
RHOA, a founding member of the Rho GTPase family, is critical for actomyosin dynamics, polarity, and morphogenesis in response to developmental cues, mechanical stress, and inflammation. In murine small intestinal epithelium, inducible RHOA deletion causes a loss of epithelial polarity, with disrupted villi and crypt organization. In the intestinal crypts, RHOA deficiency results in reduced cell proliferation, increased apoptosis, and a loss of intestinal stem cells (ISCs) that mimic effects of radiation damage...
November 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29129556/mechanisms-of-rhoa-inactivation-and-cdc42-and-rac1-activation-during-zebrafish-optic-nerve-regeneration
#15
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/29129293/the-phenotype-of-peritoneal-mouse-macrophages-depends-on-the-mitochondria-and-atp-adp-homeostasis
#16
Wei Chen, Hector Sandoval, Jacek Z Kubiak, Xian C Li, Rafik M Ghobrial, Malgorzata Kloc
Different macrophage subtypes have different morphologies/shapes and functions. Naïve M0 macrophages are elongated. Pro-inflammatory M1 that produce the bactericidal molecule iNos are round. Anti-inflammatory M2 macrophages that produce the pro-healing enzyme Arg-1 are highly elongated. We showed previously that the morphologies of M0 and M2 but not M1 macrophages are RhoA-dependent. Macrophage-specific deletion of RhoA causes the extreme elongation (hummingbird phenotype) of M0 and M2 but not M1 macrophages...
November 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29125993/substrate-and-mechanotransduction-influence-serca2a-localization-in-human-pluripotent-stem-cell-derived-cardiomyocytes-affecting-functional-performance
#17
Sebastian Martewicz, Elena Serena, Susi Zatti, Gordon Keller, Nicola Elvassore
Physical cues are major determinants of cellular phenotype and evoke physiological and pathological responses on cell structure and function. Cellular models aim to recapitulate basic functional features of their in vivo counterparts or tissues in order to be of use in in vitro disease modeling or drug screening and testing. Understanding how culture systems affect in vitro development of human pluripotent stem cell (hPSC)-derivatives allows optimization of cellular human models and gives insight in the processes involved in their structural organization and function...
October 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29124866/characterization-of-the-toxin-plx2a-a-rhoa-targeting-adp-ribosyltransferase-produced-by-the-honey-bee-pathogen-paenibacillus-larvae
#18
Julia Ebeling, Anne Fünfhaus, Henriette Knispel, Dan Krska, Ravikiran Ravulapalli, Kayla A Heney, Miguel R Lugo, A Rod Merrill, Elke Genersch
The toxin Plx2A is an important virulence factor of Paenibacillus larvae, the etiological agent of American Foulbrood, the most destructive bacterial disease of honey bees. Biochemical and functional analyses as well as the crystal structure of Plx2A revealed that it belongs to the C3 mono-ADP-ribosylating toxin subgroup. RhoA was identified as the cellular target of Plx2A activity. The kinetic parameters (KM, kcat) were established for both the transferase and glycohydrolase (GH) reactions. When expressed in yeast, Plx2A was cytotoxic for eukaryotic cells and catalytic variants confirmed that the cytotoxicity of Plx2A depends on its enzymatic activity...
November 10, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/29122888/tnf-stimulated-gene-6-promotes-formation-of-hyaluronan-inter-%C3%AE-inhibitor-heavy-chain-complexes-necessary-for-ozone-induced-airway-hyperresponsiveness
#19
Vandy P Stober, Collin G Johnson, Alana Majors, Mark E Lauer, Valbona Cali, Ronald J Midura, Hans-Georg Wisniewski, Mark A Aronica, Stavros Garantziotis
Exposure to pollutants, such as ozone, exacerbates airway inflammation and hyperresponsiveness (AHR). TNF-stimulated gene 6 (TSG-6) is required to transfer inter-α-inhibitor heavy chains (HC) to hyaluronan (HA), facilitating HA receptors binding. TSG-6 is necessary for AHR in allergic asthma, because it facilitates the development of a pathological HA-HC matrix. However, the role of TSG-6 in acute airway inflammation is not well understood. Here, we hypothesized that TSG-6 is essential for the development of HA- and ozone-induced AHR...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29121972/long-noncoding-rna-norad-a-novel-competing-endogenous-rna-enhances-the-hypoxia-induced-epithelial-mesenchymal-transition-to-promote-metastasis-in-pancreatic-cancer
#20
Hongzhe Li, Xinjing Wang, Chenlei Wen, Zhen Huo, Weishen Wang, Qian Zhan, Dongfeng Cheng, Hao Chen, Xiaxing Deng, Chenghong Peng, Baiyong Shen
BACKGROUND: Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown...
November 9, 2017: Molecular Cancer
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