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rho kinase and protein aggregation

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https://www.readbyqxmd.com/read/27768934/the-proteasome-regulates-collagen-induced-platelet-aggregation-via-nuclear-factor-kappa-b-nf%C3%A4-b-activation
#1
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27502036/lh-and-fsh-promote-migration-and-invasion-properties-of-a-breast-cancer-cell-line-through-regulatory-actions-on-the-actin-cytoskeleton
#2
Angel Matias Sanchez, Marina Ines Flamini, Eleonora Russo, Elena Casarosa, Simone Pacini, Mario Petrini, Andrea Riccardo Genazzani, Tommaso Simoncini
Reproductive hormones influence breast cancer development and progression. While the actions of sex steroids in this setting are established, tentative evidence suggests that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may also play a role, yet this remains elusive. We here identify that T-47D breast cancer cells express functional receptors for FSH and LH, and that these hormones regulate breast cancer cell motility and invasion through the control of the actin cytoskeleton and the formation of cortical actin aggregates and focal adhesion complexes...
December 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27312222/cadherin-11-overexpression-induces-extracellular-matrix-remodeling-and-calcification-in-mature-aortic-valves
#3
Derek C Sung, Caitlin J Bowen, Kiran A Vaidya, Jingjing Zhou, Nikita Chapurin, Andrew Recknagel, Bin Zhou, Jonathan Chen, Michael Kotlikoff, Jonathan T Butcher
OBJECTIVE: Calcific aortic valve (AoV) disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. Enhanced cell-cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. Cadherin-11 (Cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. This study aims to elucidate the specific functions of Cad-11 and its downstream targets, RhoA and Sox9, in extracellular matrix remodeling and AoV calcification...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27101974/fasudil-attenuates-aggregation-of-%C3%AE-synuclein-in-models-of-parkinson-s-disease
#4
Lars Tatenhorst, Katrin Eckermann, Vivian Dambeck, Luis Fonseca-Ornelas, Hagen Walle, Tomás Lopes da Fonseca, Jan C Koch, Stefan Becker, Lars Tönges, Mathias Bähr, Tiago F Outeiro, Markus Zweckstetter, Paul Lingor
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet disease-modifying treatments do not currently exist. Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. Since alpha-synuclein (α-Syn) aggregation is a major hallmark in the pathogenesis of PD, we aimed to evaluate the anti-aggregative potential of pharmacological ROCK inhibition using the isoquinoline derivative Fasudil, a small molecule inhibitor already approved for clinical use in humans...
April 22, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27003208/expression-of-tau-produces-aberrant-plasma-membrane-blebbing-in-glial-cells-through-rhoa-rock-dependent-f-actin-remodeling
#5
Francisco M Torres-Cruz, Fanny Rodríguez-Cruz, Jaime Escobar-Herrera, Norma Barragán-Andrade, Gustavo Basurto-Islas, Daniela Ripova, Jesús Ávila, Francisco Garcia-Sierra
Abnormal aggregation of Tau in glial cells has been reported in Alzheimer's disease (AD) and other tauopathies; however, the pathological significance of these aggregates remains unsolved to date. In this study, we evaluated whether full-length Tau (Tau441) and its aspartic acid421-truncated Tau variant (Tau421) produce alterations in the normal organization of the cytoskeleton and plasma membrane (PM) when transiently expressed in cultured C6-glial cells. Forty-eight hours post-transfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421...
March 21, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/26700725/ptp1b-triggers-integrin-mediated-repression-of-myosin-activity-and-modulates-cell-contractility
#6
Ana E González Wusener, Ángela González, Fumihiko Nakamura, Carlos O Arregui
Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium...
2015: Biology Open
https://www.readbyqxmd.com/read/26683082/fasudil-a-rho-kinase-inhibitor-promotes-the-autophagic-degradation-of-a53t-%C3%AE-synuclein-by-activating-the-jnk-1-bcl-2-beclin-1-pathway
#7
Feng-Tao Liu, Yu-Jie Yang, Jian-Jun Wu, Shan Li, Yi-Lin Tang, Jue Zhao, Zhen-Yang Liu, Bao-Guo Xiao, Ji Zuo, Wen Liu, Jian Wang
Accumulation of α-synuclein (α-syn) is pivotally implicated in the pathogenesis of Parkinson׳s disease (PD), and enhancing its clearance might be a promising strategy in PD treatment. It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. However, it is not known if fasudil, the only ROCK inhibitor available in clinical setting, could promote the degradation of α-syn, and ameliorate the α-syn induced neurotoxicity...
February 1, 2016: Brain Research
https://www.readbyqxmd.com/read/26592750/inhibition-of-rho-associated-protein-kinase-increases-the-angiogenic-potential-of-mesenchymal-stem-cell-aggregates-via-paracrine-effects
#8
Soyoung Hong, Jae Yeon Lee, Changmo Hwang, Jennifer H Shin, Yongdoo Park
The aggregation of multiple cells, such as mesenchymal condensation, is an important biological process in skeletal muscle development, osteogenesis, and adipogenesis. Due to limited in vivo study model systems, a simple and effective in vitro three-dimensional (3D) aggregation system is required to study the mechanisms of multicellular aggregation and its applications. We first generated controlled mesenchymal stem cell (MSC) aggregates using a bioprinting technique to monitor their aggregation and sprouting...
February 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/26346982/calycosin-7-o-%C3%AE-d-glucoside-promotes-oxidative-stress-induced-cytoskeleton-reorganization-through-integrin-linked-kinase-signaling-pathway-in-vascular-endothelial-cells
#9
Yue-Hua Jiang, Wei Sun, Wei Li, Hong-Zhen Hu, Le Zhou, Hui-Hui Jiang, Jing-Xin Xu
BACKGROUND: Dysfunction of vascular endothelium is implicated in many pathological situations. Cytoskeleton plays an importance role in vascular endothelial permeability barrier and inflammatory response. Many Chinese herbs have the endothelial protective effect, of which, "Astragalus membranaceus" is a highly valued herb for treatment of cardiovascular and renal diseases in traditional Chinese medicine, In this study, we tested whether calycosin-7-O-β-D-glucoside (Calycosin), a main effective monomer component of "Astragalus membranaceus", could protect endothelial cells from bacterial endotoxin (LPS)-induced cell injury...
2015: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/26215804/attenuated-platelet-aggregation-in-patients-with-septic-shock-is-independent-from-the-activity-state-of-myosin-light-chain-phosphorylation-or-a-reduction-in-rho-kinase-dependent-inhibition-of-myosin-light-chain-phosphatase
#10
Benjamin Aj Reddi, Samantha M Iannella, Stephanie N O'Connor, Adam M Deane, Scott R Willoughby, David P Wilson
BACKGROUND: Impaired coagulation contributes to the morbidity and mortality associated with septic shock. Whether abnormal platelet contraction adds to the bleeding tendency is unknown. Platelets contract when Ca(2+)-dependent myosin light chain kinase (MLCK) phosphorylates Ser19 of myosin light chain (MLC20), promoting actin-myosin cross-bridge cycling. Contraction is opposed when myosin light chain phosphatase (MLCP) dephosphorylates MLC20. It is thought that Rho kinase (ROK) inhibits MLCP by phosphorylating Thr855 of the regulatory subunit MYPT, favouring platelet contraction...
December 2015: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/25500336/rho-kinase-regulates-human-platelet-activation-induced-by-thromboxane-a2-independently-of-p38-map-kinase
#11
Yuko Iida, Tomoaki Doi, Haruhiko Tokuda, Rie Matsushima-Nishiwaki, Masanori Tsujimoto, Gen Kuroyanagi, Naohiro Yamamoto, Yukiko Enomoto, Kumiko Tanabe, Takanobu Otsuka, Toru Iwama, Shinji Ogura, Osamu Kozawa, Hiroki Iida
We have previously demonstrated that ristocetin, an activator of GPIb/IX/V, induces the release of soluble CD40 ligand (sCD40L) via thromboxane A2 production in human platelets. It has been shown that thromboxane A2 induces the activation of Rho-kinase, a downstream effector of Rho, in human platelets. In the present study, we investigated the exact roles of Rho-kinase in thromboxane A2-induced platelet activation. We found that U46619, a thromboxane receptor (TP) agonist, induced the phosphorylation of cofilin, a target of Rho-kinase signaling, and that the cofilin phosphorylation by U46619 was suppressed by Y27632 or fasudil, specific inhibitors of Rho-kinase...
March 2015: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/25445826/rhoa-signaling-through-platelet-p2y%C3%A2-receptor-controls-leukocyte-recruitment-in-allergic-mice
#12
Richard T Amison, Stefania Momi, Abigail Morris, Giorgia Manni, Sandra Keir, Paolo Gresele, Clive P Page, Simon C Pitchford
BACKGROUND: Clinical studies reveal platelet activation in patients with asthma, allergic rhinitis, and eczema. This is distinct from platelet aggregation, which is critical for the maintenance of hemostasis and in which a role for platelet purinergic receptors is well documented. However, purines are also essential for inflammatory cell trafficking in animal models of allergic lung inflammation, which are known to be platelet dependent, yet the role of purines in the platelet activation accompanying inflammation is unknown...
February 2015: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/25212232/disabled-2-is-required-for-efficient-hemostasis-and-platelet-activation-by-thrombin-in-mice
#13
Hui-Ju Tsai, Chien-Ling Huang, Yao-Wen Chang, Ding-Yuan Huang, Chung-Ching Lin, Jonathan A Cooper, Ju-Chien Cheng, Ching-Ping Tseng
OBJECTIVE: The essential role of platelet activation in hemostasis and thrombotic diseases focuses attention on unveiling the underlying intracellular signals of platelet activation. Disabled-2 (Dab2) has been implicated in platelet aggregation and in the control of clotting responses. However, there is not yet any in vivo study to provide direct evidence for the role of Dab2 in hemostasis and platelet activation. APPROACH AND RESULTS: Megakaryocyte lineage-restricted Dab2 knockout (Dab2(-/-)) mice were generated to delineate in vivo functions of Dab2 in platelets...
November 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/25150189/p38mapk-rho-rock-and-pkc-pathways-are-involved-in-influenza-induced-cytoskeletal-rearrangement-and-hyperpermeability-in-pmvec-via-phosphorylating-erm
#14
Chenyue Zhang, Ying Wu, Zinan Xuan, Shujing Zhang, Xudan Wang, Yu Hao, Jun Wu, Shu Zhang
Severe influenza infections are featured by acute lung injury, a syndrome of pulmonary microvascular leak. A growing number of evidences have shown that the pulmonary microvascular endothelial cells (PMVEC) are critical target of influenza virus, promoting microvascular leak. It is reported that there are multiple mechanisms by which influenza virus could elicit increased pulmonary endothelial permeability, in both direct and indirect manners. Ezrin/radixin/moesin family proteins, the linkers between plasma membrane and actin cytoskeleton, have been reported to be involved in cell adhesion, motility and may modulate endothelial permeability...
November 4, 2014: Virus Research
https://www.readbyqxmd.com/read/25147500/interleukin-18-alters-protein-expressions-of-neurodegenerative-diseases-linked-proteins-in-human-sh-sy5y-neuron-like-cells
#15
Elina M Sutinen, Minna A Korolainen, Jukka Häyrinen, Irina Alafuzoff, Steven Petratos, Antero Salminen, Hilkka Soininen, Tuula Pirttilä, Johanna O Ojala
Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity...
2014: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/25129107/involvement-of-rhoa-rock-in-insulin-secretion-of-pancreatic-%C3%AE-cells-in-3d-culture
#16
Xiaofang Liu, Fang Yan, Hailei Yao, Mingyang Chang, Jinhua Qin, Yali Li, Yunfang Wang, Xuetao Pei
Cell-cell contacts and interactions between pancreatic β-cells and/or other cell populations within islets are essential for cell survival, insulin secretion, and functional synchronization. Three-dimensional (3D) culture systems supply the ideal microenvironment for islet-like cluster formation and functional maintenance. However, the underlying mechanisms remain unclear. In this study, mouse insulinoma 6 (MIN6) cells were cultured in a rotating 3D culture system to form islet-like aggregates. Glucose-stimulated insulin secretion (GSIS) and the RhoA/ROCK pathway were investigated...
November 2014: Cell and Tissue Research
https://www.readbyqxmd.com/read/25073288/-effect-of-mechanical-tension-on-expressions-of-rhoa-rho-associated-protein-kinases-in-rat-tendon-stem-cells-in-vitro
#17
Lin Ma, Kanglai Tang, Binghua Zhou, Guanghua Yang, Wan Chen, Miduo Mu, Chengsong Yuan
OBJECTIVE: To investigate the effect of different mechanical tensions on the expressions of RhoA/Rho associated protein kinases (ROCK) in rat tendon stem cells (TSCs). METHODS: TSCs were isolated from the tendon tissue of male Sprague Dawley rats (aged, 2-3 months; weighing, 200-250 g) by enzymatic digestion method and cultured for 2-3 passages, then seeded on micro groovdishes. The 4% (4% stretch group) and 8% (8% stretch group) mechanical stretching was performed for 4 hours every day at 1 Hz...
May 2014: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/25068972/effect-of-2-arachidonoylglycerol-on-myosin-light-chain-phosphorylation-and-platelet-activation-the-role-of-phosphatidylinositol-3-kinase-akt-pathway
#18
Maria Grazia Signorello, Giuliana Leoncini
The endocannabinoid 2-arachidonoylglycerol (2-AG) can be considered a true agonist as it is able to activate human platelets stimulating arachidonic acid release, thromboxane B2 formation and calcium intracellular elevation. Recently we have shown that 2-AG induces a rapid myosin light chain (MLC) phosphorylation/activation, early mediated by RhoA kinase (ROCK) signalling pathway and later by myosin light chain kinase. The aim of the present study was to investigate the role of phosphatidylinositol 3 kinase (PI3K)/AKT pathway in MLC phosphorylation and some downstream events such as actin polymerization, ATP secretion and aggregation...
October 2014: Biochimie
https://www.readbyqxmd.com/read/24923466/ca2-influx-through-p2x1-receptors-amplifies-p2y1-receptor-evoked-ca2-signaling-and-adp-evoked-platelet-aggregation
#19
Sarah Jones, Richard J Evans, Martyn P Mahaut-Smith
Many cells express both P2X cation channels and P2Y G-protein-coupled receptors that are costimulated by nucleotides released during physiologic or pathophysiologic responses. For example, during hemostasis and thrombosis, ATP-gated P2X1 channels and ADP-stimulated P2Y1 and P2Y12 G-protein coupled receptors play important roles in platelet activation. It has previously been reported that P2X1 receptors amplify P2Y1-evoked Ca(2+) responses in platelets, but the underlying mechanism and influence on function is unknown...
September 2014: Molecular Pharmacology
https://www.readbyqxmd.com/read/24901221/pink1-mediated-phosphorylation-of-parkin-boosts-parkin-activity-in-drosophila
#20
Kahori Shiba-Fukushima, Tsuyoshi Inoshita, Nobutaka Hattori, Yuzuru Imai
Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is involved in mitochondrial maintenance and activity of dopaminergic neurons in vivo. Here, we examined the effects of Parkin phosphorylation in Drosophila, in which the phosphorylation residue is conserved at Ser94...
June 2014: PLoS Genetics
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