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https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#1
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/29153889/3d-qsar-studies-on-indole-and-7-azoindole-derivatives-as-rock-2-inhibitors-an-integrative-computational-approach
#2
Santhosh Kumar Nagarajan, Sathya Babu, Honglae Sohn, Panneer Devaraju, Thirumurthy Madhavan
Rho Kinases (ROCK) has been found to regulate a wide range of fundamental cell functions such as contraction, motility, proliferation, and apoptosis. Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states. In this study, we have performed pharmacophore modeling and 3D QSAR studies on a series of 36 indoles and 7-azoindoles derivatives as ROCK2 inhibitors to elucidate the structural variations with their inhibitory activities...
October 9, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29152648/melatonin-inhibits-colon-cancer-rko-cell-migration-by-downregulating-rho%C3%A2-associated-protein-kinase-expression-via-the-p38-mapk-signaling-pathway
#3
Zhen Liu, Duobing Zou, Xiaoping Yang, Xiaolong Xue, Li Zuo, Qing Zhou, Ruolei Hu, Yuan Wang
Melatonin is predominately produced and secreted by the pineal gland, and inhibits cell growth in various cancer cell lines such as colorectal cancer. However, the precise mechanisms involved have not been fully elucidated. In the present study, the potential molecular mechanism underlying the efficacy of melatonin on migration in RKO colon cancer cells was investigated. The effects of melatonin and H‑1152, a selective inhibitor of Rho‑associated protein kinase (ROCK), on the migration of RKO cells were analyzed by an in vitro wound healing assay...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#4
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/29135354/depression-following-traumatic-brain-injury-in-mice-is-associated-with-down-regulation-of-hippocampal-astrocyte-glutamate-transporters-by-thrombin
#5
Chun-Shu Piao, Ashley L Holloway, Sue Hong-Routson, Mark S Wainwright
Depression after traumatic brain injury (TBI) is common but the mechanisms by which TBI causes depression are unknown. TBI decreases glutamate transporters GLT-1 and GLAST and allows extravasation of thrombin. We examined the effects of thrombin on transporter expression in primary hippocampal astrocytes. Application of a PAR-1 agonist caused down-regulation of GLT-1, which was prevented by inhibition of Rho kinase (ROCK). To confirm these mechanisms in vivo, we subjected mice to closed-skull TBI. Thrombin activity in the hippocampus increased one day following TBI...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29130932/p120-catenin-is-an-obligate-haploinsufficient-tumor-suppressor-in-intestinal-neoplasia
#6
Sarah P Short, Jumpei Kondo, Whitney G Smalley-Freed, Haruna Takeda, Michael R Dohn, Anne E Powell, Robert H Carnahan, Mary K Washington, Manish Tripathi, D Michael Payne, Nancy A Jenkins, Neal G Copeland, Robert J Coffey, Albert B Reynolds
p120-Catenin (p120) functions as a tumor suppressor in intestinal cancer, but the mechanism is unclear. Here, using conditional p120 knockout in Apc-sensitized mouse models of intestinal cancer, we have identified p120 as an "obligatory" haploinsufficient tumor suppressor. Whereas monoallelic loss of p120 was associated with a significant increase in tumor multiplicity, loss of both alleles was never observed in tumors from these mice. Moreover, forced ablation of the second allele did not further enhance tumorigenesis, but instead induced synthetic lethality in combination with Apc loss of heterozygosity...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29125993/substrate-and-mechanotransduction-influence-serca2a-localization-in-human-pluripotent-stem-cell-derived-cardiomyocytes-affecting-functional-performance
#7
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/29125705/m-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signaling-pathway
#8
Yong Zhang, Jie Li, Bingxi Li, Jing Wang, Cui Hua Liu
Establishment of infection by facultative intracellular pathogen Mycobacterium tuberculosis (Mtb) requires adherence to and internalization by macrophages. However, the effector molecules exploited by Mtb for entry into macrophages remain to be fully understood. The mammalian cell entry (Mce) proteins play an essential role in facilitating the internalization of mycobacteria into mammalian cells. Here we characterized Mtb Mce3C as a new mycobacterial surface protein that could promote mycobacterial adhesion to and invasion of macrophages in an RGD motif-dependent manner...
November 10, 2017: Cellular 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
#9
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/29119680/nicorandil-regulates-the-macrophage-skewing-and-ameliorates-myofibroblasts-by-inhibition-of-rhoa-rho-kinase-signalling-in-infarcted-rats
#10
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
We have demonstrated that ATP-sensitive potassium (KATP ) channel agonists attenuated fibrosis; however, the mechanism remained unclear. Since RhoA has been identified as a mediator of cardiac fibrosis, we sought to determine whether the anti-fibrotic effects of KATP channel agonists were mediated via regulating macrophage phenotype and fibroblast differentiation by a RhoA/RhoA-kinase-dependent pathway. Wistar male rats after induction of myocardial infarction were randomized to either vehicle, nicorandil, an antagonist of KATP channel glibenclamide, an antagonist of ROCK fasudil, or a combination of nicorandil and glibenclamide or fasudil and glibenclamide starting 24 hrs after infarction...
November 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29115372/inhibition-of-rho-kinase-protects-against-colitis-in-mice-by-attenuating-intestinal-epithelial-barrier-dysfunction-via-mlc-and-the-nf-%C3%AE%C2%BAb-pathway
#11
Yanting Zou, Lili Ma, Yuan Zhao, Shuncai Zhang, Chaohui Zhou, Yu Cai
The aim of the present study was to investigate the role of Rho kinase (also known as ROCK) inhibitor in 2,4,6-trinitrobenzene sulfonic acid induced mouse colitis; and to elucidate the underlying mechanism of ROCK1/ROCK2 inhibition in enhancing intestinal epithelial barrier (IEB) function. A specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in mouse colitis models. ROCK1 and ROCK2 were silenced respectively using RNA interference in Caco-2 cells. The expression of tight junction proteins and the downstream molecules of ROCK were assessed...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29098568/the-signaling-of-protease-activated-receptor-2-activating-peptide-induced-contraction-in-cat-esophageal-smooth-muscle-cells
#12
Hyun Su Ha, Se Eun Lee, Hyun Seok Lee, Gil Hyung Kim, Chan Jong Yoon, Jong Soo Han, Ji-Yun Lee, Uy Dong Sohn
Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis...
November 2, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29096761/profilin-1-plays-feedback-role-in-actin-mediated-polar-body-extrusion-in-mouse-oocytes
#13
Jun Liu, Qiao-Chu Wang, Xing Duan, Xiang-Shun Cui, Nam-Hyung Kim, Yu Zhang, Shao-Chen Sun
Mammalian oocytes undergo several crucial processes during meiosis maturation, including spindle formation and migration and polar body extrusion, which rely on the regulation of actin. As a small actin-binding protein, profilin 1 plays a central role in the regulation of actin assembly. However, the functions of profilin 1 in mammalian oocytes are uncertain. To investigate the function of profilin 1 in oocytes, immunofluorescent staining was first used to examine profilin 1 localisation. The results showed that profilin 1 was localised around the meiotic spindles and was colocalised with cytoplasmic actin...
November 3, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29084331/the-anti-inflammatory-effect-of-ripasudil-k-115-a-rho-kinase-rock-inhibitor-on-endotoxin-induced-uveitis-in-rats
#14
Takatoshi Uchida, Megumi Honjo, Reiko Yamagishi, Makoto Aihara
Purpose: To investigate the anti-inflammatory properties of ripasudil, a Rho kinase (ROCK) inhibitor, using endotoxin-induced uveitis (EIU) in rats. Methods: Endotoxin-induced uveitis was induced by footpad injection of lipopolysaccharide (LPS). Ripasudil was administered intraperitoneally 1 hour before and after LPS injection. The aqueous humor was collected 24 hours after injection, and the infiltrating cells, protein concentration, and levels of monocyte chemotactic protein-1 (MCP-1) were determined...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29075304/effects-of-gualou-guizhi-decoction-aqueous-extract-on-axonal-regeneration-in-organotypic-cortical-slice-culture-after-oxygen-glucose-deprivation
#15
Lihong Nan, Lan Yang, Yanfang Zheng, Yibo He, Qingqing Xie, Zheming Chen, Huang Li, Mei Huang
Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29061365/rho-specific-guanine-nucleotide-exchange-factors-rho-gefs-inhibition-affects-macrophage-phenotype-and-disrupts-golgi-complex
#16
Wei Chen, Yue Zhao, Xian C Li, Jacek Z Kubiak, Rafik M Ghobrial, Malgorzata Kloc
Macrophages play crucial role in tissue homeostasis and the innate and adaptive immune response. Depending on the state of activation macrophages acquire distinct phenotypes that depend on actin, which is regulated by small GTPase RhoA. The naive M0 macrophages are slightly elongated, pro-inflammatory M1 are round and M2 anti-inflammatory macrophages are elongated. We showed previously that interference with RhoA pathway (RhoA deletion or RhoA/ROCK kinase inhibition) disrupted actin, produced extremely elongated (hummingbird) macrophage phenotype and inhibited macrophage movement toward transplanted hearts...
October 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29059211/screening-differential-mirnas-responsible-for-permeability-increase-in-huvecs-infected-with-influenza-a-virus
#17
Shujing Zhang, Ying Wu, Zinan Xuan, Xiaoming Chen, Junjie Zhang, Dongyu Ge, Xudan Wang
Severe influenza infections are featured by acute lung injury, a syndrome of increased pulmonary microvascular permeability. A growing number of evidences have shown that influenza A virus induces cytoskeletal rearrangement and permeability increase in endothelial cells. Although miRNA's involvement in the regulation of influenza virus infection and endothelial cell (EC) function has been well documented, little is known about the miRNA profiles in influenza-infected endothelial cells. Using human umbilical vein endothelial cells (HUVECs) as cell models, the present study aims to explore the differential miRNAs in influenza virus-infected ECs and analyze their target genes involved in EC permeability regulation...
2017: PloS One
https://www.readbyqxmd.com/read/29059167/loss-of-rhoa-promotes-skin-tumor-formation-and-invasion-by-upregulation-of-rhob
#18
A García-Mariscal, H Li, E Pedersen, K Peyrollier, K M Ryan, A Stanley, F Quondamatteo, C Brakebusch
Cellular movement is controlled by small GTPases, such as RhoA. Although migration is crucial for cancer cell invasion, the specific role of RhoA in tumor formation is unclear. Inducing skin tumors in mice with a keratinocyte-restricted loss of RhoA, we observed increased tumor frequency, growth and invasion. In vitro invasion assays revealed that in the absence of RhoA cell invasiveness is increased in a Rho-associated protein kinase (ROCK) activation and cell contraction-dependent manner. Surprisingly, loss of RhoA causes increased Rho signaling via overcompensation by RhoB because of reduced lysosomal degradation of RhoB in Gamma-aminobutyric acid receptor-associated protein (GABARAP)+ autophagosomes and endosomes...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29057980/rock-inhibition-with-fasudil-induces-beta-catenin-nuclear-translocation-and-inhibits-cell-migration-of-mda-mb-231-human-breast-cancer-cells
#19
Fabiana Sélos Guerra, Ramon Guerra de Oliveira, Carlos Alberto Manssour Fraga, Claudia Dos Santos Mermelstein, Patricia Dias Fernandes
Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29057688/rock-as-a-therapeutic-target-for-ischemic-stroke
#20
Nikola Sladojevic, Brian Yu, James K Liao
Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology...
October 30, 2017: Expert Review of Neurotherapeutics
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