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https://www.readbyqxmd.com/read/29782855/role-of-statins-and-mevalonate-pathway-on-impaired-hdac2-activity-induced-by-oxidative-stress-in-human-airway-epithelial-cells
#1
Maria Gabriella Matera, Luigino Calzetta, Giulia Gritti, Laura Gallo, Brunella Perfetto, Giovanna Donnarumma, Mario Cazzola, Paola Rogliani, Maria Donniacuo, Barbara Rinaldi
In patients with chronic obstructive pulmonary disease (COPD) the inflammatory response is often steroid-resistant, likely since oxidative stress and cigarette smoking impair histone deacetylase 2 (HDAC2) activity. Since it has been demonstrated that statins may restore the HDAC2 activity in cultured human endothelial cells, the aim of this study was to investigate the effects of statins in reversing the steroid-resistance induced by oxidative stress. We evaluated the effects of simvastatin and dexamethasone on HDAC2 expression and activity, and the role of mevalonate and Rho/ROCK pathways in A549 cells, a human lung type II epithelial cell line stressed with H2 O2 ...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29777035/septin-dependent-remodeling-of-cortical-microtubule-drives-cell-reshaping-during-epithelial-wound-healing
#2
Asako Shindo, Anastasia Audrey, Maki Takagishi, Masahide Takahashi, John B Wallingford, Makoto Kinoshita
Wounds in embryos heal rapidly through the contraction of the wound edges. Despite well-recognized significance of the actomyosin purse-string for wound closure, roles for other cytoskeletal components are largely unknown. Here, we report that the septin cytoskeleton cooperates with actomyosin and microtubules to coordinate circumferential contraction of the wound margin and concentric elongation of wound-proximal cells in Xenopus laevis embryos. Microtubules reoriented radially, forming bundles along lateral cell cortices in elongating wound-proximal cells...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29774524/%C3%AE-e-catenin-is-a-candidate-tumor-suppressor-for-the-development-of-e-cadherin-expressing-lobular-type-breast-cancer
#3
Jolien S de Groot, Max A K Rätze, Miranda van Amersfoort, Tanja Eisemann, Eva J Vlug, Mijanou T Niklaas, Suet-Feung Chin, Carlos Caldas, Paul J van Diest, Jos Jonkers, Johan de Rooij, Patrick W B Derksen
Mutational inactivation of E-cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), although approximately 10-15% of all ILCs retain membrane-localized E-cadherin, despite the presence of an apparent non-cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α-catenin (CTNNA1) loss in the regulation of anchorage independence of non-invasive breast carcinoma...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29767957/magnetic-manipulation-of-reversible-nanocaging-controls-in-vivo-adhesion-and-polarization-of-macrophages
#4
Heemin Kang, Hee Joon Jung, Sung Kyu Kim, Dexter Siu Hong Wong, Sien Lin, Gang Li, Vinayak P Dravid, Liming Bian
Macrophages are key immune cells that perform various physiological functions, such as the maintenance of homeostasis, host defense, disease progression, and tissue regeneration. Macrophages adopt distinctly polarized phenotypes, such as pro-inflammatory M1 phenotype or anti-inflammatory (pro-healing) M2 phenotype, to execute disparate functions. The remotely controlled reversible uncaging of bioactive ligands, such as Arg-Gly-Asp (RGD) peptide, is an appealing approach for temporally regulating the adhesion and resultant polarization of macrophages on the implants in vivo...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29766980/ripasudil-attenuates-lipopolysaccharide-lps-mediated-apoptosis-and-inflammation-in-pulmonary-microvascular-endothelial-cells-via-rock2-enos-signaling
#5
Jianxin Yang, Feng Ruan, Zhongjun Zheng
BACKGROUND Microvascular endothelial inflammation and apoptosis are responsible for septic acute lung injury (ALI). Ripasudil is a novel Rho/Rho kinase (ROCK) inhibitor which shows therapeutic effects on several vascular diseases. The aim of this study was to investigate the protective effects and correlated molecular mechanisms of ripasudil on lipopolysaccharide- induced inflammation and apoptosis of pulmonary microvascular endothelial cells (PMVECs). MATERIAL AND METHODS Cultured PMVECs were exposed to lipopolysaccharide (LPS)...
May 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29756391/rho-kinase-and-na-h-exchanger-mediate-endothelin-1-induced-pulmonary-arterial-smooth-muscle-cell-proliferation-and-migration
#6
John C Huetsch, Jasmine Walker, Clark Undem, Julie Lade, Xin Yun, Syeda Baksh, Haiyang Jiang, Ning Lai, Larissa A Shimoda
Excessive production of endothelin-1 (ET-1) has been observed in almost all forms of pulmonary hypertension. ET-1, a highly potent vasoconstrictor, can also potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. Increasing evidence indicates that alkalinization of intracellular pH (pHi ), typically due to activation of Na+ /H+ exchange (NHE), is associated with enhanced PASMC proliferation and migration...
May 2018: Physiological Reports
https://www.readbyqxmd.com/read/29749605/rho-signaling-research-history-current-status-and-future-directions
#7
Shuh Narumiya, Dean Thumkeo
One of the main research areas in biology from the mid-1980's through the 990's was the elucidation of signaling pathways governing cell responses. These studies brought, among other molecules, the small GTPase Rho to the epicenter. Rho signaling research has since expanded to all areas of biology and medicine. Here, we describe how Rho emerged as a key molecule governing cell morphogenesis and movement, how it was linked to actin reorganization, and how the study of Rho signaling has expanded from cultured cells to whole biological systems...
May 10, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29749502/toll%C3%A2-like-receptor-4-promotes-the-phosphorylation-of-crmp2-via-the-activation-of-rho%C3%A2-kinase-in-mcao-rats
#8
Xue-Bo Li, Ming-Xia Ding, Chun-Li Ding, Liang-Liang Li, Jinzhou Feng, Xiao-Jun Yu
The mechanism associated with Toll‑like receptor 4 (TLR4) in neurological injury remains unclear. The aim of the present study was to investigate the pathology of TLR4 in middle cerebral artery occlusion (MCAO)/reperfusion rat models via the regulation of collapsin response mediator protein 2 (CRMP2) phosphorylation. The modified neurological severity score (mNSS) was applied to assess neurological recovery. Immunofluorescence and western blotting were used to detect the protein expressions of TLR4, Rho‑associated protein kinase 2 (ROCK‑II) and CRMP2 following the intracerebroventricular administration of TLR4‑specific agonist, lipopolysaccharide (LPS) and TLR4‑neutralizing antibody, the ROCK‑II specific inhibitor Y‑27632 or LPS+Y‑27632 30 min prior to MCAO...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#9
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29735632/endothelial-ppar%C3%AE-peroxisome-proliferator-activated-receptor-%C3%AE-is-essential-for-preventing-endothelial-dysfunction-with-aging
#10
T Michael De Silva, Ying Li, Dale A Kinzenbaw, Curt D Sigmund, Frank M Faraci
Little is known about mechanisms that control vascular aging, particularly at the cell-specific level. PPARγ (peroxisome proliferator-activated receptor-γ) exerts protective effects in the vasculature when activated pharmacologically. To gain insight into the cell-specific impact of PPARγ, we examined the hypothesis that genetic interference with endothelial PPARγ would augment age-induced vascular dysfunction. We studied carotid arteries from adult (11.6±0.3 months) and old (24.7±0.6 months) mice with endothelial-specific expression of a human dominant negative mutation in PPARγ driven by the vascular cadherin promoter (E-V290M), along with age-matched, nontransgenic littermates...
May 7, 2018: Hypertension
https://www.readbyqxmd.com/read/29734379/sphingosine-1-phosphate-attenuates-mmp2-and-mmp9-in-human-anaplastic-thyroid-cancer-c643-cells-importance-of-s1p2
#11
Muhammad Yasir Asghar, Kati Kemppainen, Taru Lassila, Kid Törnquist
In anaplastic thyroid cancer C643 cells, sphingosine 1-phosphate (S1P) attenuates migration by activating the S1P2 receptor and the Rho-ROCK pathway. In the present study, we show that stimulating C643 cells with S1P decreases the expression, secretion and activity of matrix metalloproteinase-2 (MMP2), and to a lesser extent MMP9. Using receptor-specific antagonists, and S1P2 siRNA, we showed that the inhibition of expression of MMP2 is mediated through S1P2. Furthermore, S1P inhibited calpain activity, and inhibiting calpain pharmacologically, inhibited the effect of S1P on MMP2 expression and activity, and on MMP9 activity...
2018: PloS One
https://www.readbyqxmd.com/read/29731830/rho-rho-associated-protein-kinase-signaling-pathway-mediated-downregulation-of-runt-related-transcription-factor-2-expression-promotes-the-differentiation-of-dental-pulp-stem-cells-into-odontoblasts
#12
Xiaoqing Huang, Xiaoling Chen, Hongbai Chen, Dongwei Xu, Chen Lin, Bin Peng
The present study investigated the role of runt-related transcription factor 2 (Runx2) in regulating the differentiation of human dental pulp stem cells (hDPSCs) into odontoblasts under the mediation of the Rho/Rho-associated protein kinase (ROCK) signaling pathway. hDPSCs and human bone marrow mesenchymal stem cells (hBMSCs) were mineralized to induce differentiation. The expression levels of odontoblast- and osteoblast-specific proteins, dentin sialophosphoprotein (DSPP), osteocalcin (OCN) and Runx2, were measured using western blot analysis...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29722320/the-rho-associated-kinase-inhibitors-y27632-and-fasudil-promote-microglial-migration-in-the-spinal-cord-via-the-erk-signaling-pathway
#13
Pei-Cai Fu, Rong-Hua Tang, Zhi-Yuan Yu, Min-Jie Xie, Wei Wang, Xiang Luo
Rho-associated kinase (ROCK) is a key regulatory protein involved in inflammatory secretion in microglia in the central nervous system. Our previous studies showed that ROCK inhibition enhances phagocytic activity in microglia through the extracellular signal-regulated kinase (ERK) signaling pathway, but its effect on microglial migration was unknown. Therefore, in this study, we investigated the effects of the ROCK inhibitors Y27632 and fasudil on the migratory activity of primary cultured microglia isolated from the spinal cord, and we examined the underlying mechanisms...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29720560/targeting-the-mevalonate-pathway-suppresses-vhl-deficient-cc-rcc-through-a-hif-dependent-mechanism
#14
Jordan M Thompson, Alejandro Alvarez, Monika K Singha, Matthew W Pavesic, Quy H Nguyen, Luke J Nelson, David A Fruman, Olga V Razorenova
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins...
May 2, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29686359/direct-multiplex-imaging-and-optogenetics-of-rho-gtpases-enabled-by-near-infrared-fret
#15
Daria M Shcherbakova, Natasha Cox Cammer, Tsipora M Huisman, Vladislav V Verkhusha, Louis Hodgson
Direct visualization and light control of several cellular processes is a challenge, owing to the spectral overlap of available genetically encoded probes. Here we report the most red-shifted monomeric near-infrared (NIR) fluorescent protein, miRFP720, and the fully NIR Förster resonance energy transfer (FRET) pair miRFP670-miRFP720, which together enabled design of biosensors compatible with CFP-YFP imaging and blue-green optogenetic tools. We developed a NIR biosensor for Rac1 GTPase and demonstrated its use in multiplexed imaging and light control of Rho GTPase signaling pathways...
April 23, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29684861/inhibition-of-gastric-cancer-by-local-anesthetic-bupivacaine-through-multiple-mechanisms-independent-of-sodium-channel-blockade
#16
Jiapeng Dan, Xiaodan Gong, Dezhan Li, Guanhua Zhu, Lishen Wang, Fang Li
BACKGROUND: Retrospective studies of patients undergoing cancer surgery suggest the use of local anesthesia may decrease tumor recurrence and improve survival. The mechanisms on the benefits of local anesthesia on cancer recurrence are complex and remain to be elucidated. METHODS: This study investigated the effects of bupivacaine on various cellular activities of gastric cancer using proliferation, migration, apoptosis assay. The underlying mechanism was analyzed focusing on mitochondrial functions and the activities of Rho family members...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29678838/rho-associated-protein-kinase-1-mediates-the-regulation-of-inflammatory-markers-in-diabetic-retina-and-in-retinal-m%C3%A3-ller-cells
#17
Ghulam Mohammad, Heba Mowafak AlSharif, Mohammad Mairaj Siddiquei, Ajmal Ahmad, Kaiser Alam, Ahmed M Abu El-Asrar
GOAL: To investigate the effects of blocking Rho kinase pathway on the expression of inflammatory signaling pathways in the retina of diabetic mice and in human retinal Müller glial cells stimulated with high-glucose to replicate hyperglycemia. PROCEDURES: Retinas from diabetic mice and human retinal Müller glial cells (MIO-M1) were studied. Western blot analysis, immunofluorescence, and enzyme-linked immunosorbent assay were utilized to study the effect of the Rho kinase inhibitor fasudil on the expression of Rho-associated protein kinase-1 (ROCK-1), extracellular signal-regulated kinases1&2(ERK ½), phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-κB), inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1/CCL2)...
March 2018: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29673911/targeting-the-rhoa-rock-pathway-to-regulate-t-cell-homeostasis-in-hypoxia-induced-pulmonary-arterial-hypertension
#18
Cheng Li, Ping-Ping Liu, Dou-Dou Tang, Rong Song, Yi-Qing Zhang, Si Lei, Shang-Jie Wu
BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a crippling disease with limited therapeutic methods. The imbalance of T helper 17 cell (Th17)/regulatory T cell (Treg) plays an important role in the development of Hypoxic PAH. However, whether targeting the ras homolog family member A-Rho kinase (RhoA-ROCK) pathway (activation and inhibition) by lysophosphatidic acid (LPA) and fasudil (FSD) regulate T-cell homeostasis in Hypoxic PAH remain unknown. OBJECTIVE: To examine the effects of LPA and FSD on hypoxic pulmonary vascular remodeling and homeostasis of Th17/Treg cells in Hypoxic PAH...
April 16, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29672603/solo-a-rhoa-targeting-guanine-nucleotide-exchange-factor-is-critical-for-hemidesmosome-formation-and-acinar-development-in-epithelial-cells
#19
Sachiko Fujiwara, Tsubasa S Matsui, Kazumasa Ohashi, Shinji Deguchi, Kensaku Mizuno
Cell-substrate adhesions are essential for various physiological processes, including embryonic development and maintenance of organ functions. Hemidesmosomes (HDs) are multiprotein complexes that attach epithelial cells to the basement membrane. Formation and remodeling of HDs are dependent on the surrounding mechanical environment; however, the upstream signaling mechanisms are not well understood. We recently reported that Solo (also known as ARHGEF40), a guanine nucleotide exchange factor targeting RhoA, binds to keratin8/18 (K8/K18) intermediate filaments, and that their interaction is important for force-induced actin and keratin cytoskeletal reorganization...
2018: PloS One
https://www.readbyqxmd.com/read/29669760/rho-kinase-inhibition-by-at13148-blocks-pancreatic-ductal-adenocarinoma-invasion-and-tumor-growth
#20
Nicola Rath, June Munro, Marie Fa Cutiongco, Alicja Jagiełło, Nikolaj Gadegaard, Lynn McGarry, Mathieu Unbekandt, Evdokia Michalopoulou, Jurre J Kamphorst, David Sumpton, Gillian Mackay, Claire Vennin, Marina Pajic, Paul Timpson, Michael F Olson
The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation...
April 18, 2018: Cancer Research
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