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https://www.readbyqxmd.com/read/28088401/pharmacological-rescue-of-adult-hippocampal-neurogenesis-in-a-mouse-model-of-x-linked-intellectual-disability
#1
Manuela Allegra, Cristina Spalletti, Beatrice Vignoli, Stefano Azzimondi, Irene Busti, Pierre Billuart, Marco Canossa, Matteo Caleo
Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophn1 affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophn1 display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CA3, and showed an altered density of dendritic protrusions...
January 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28081460/blood-brain-barrier-dysfunction-induced-by-silica-nps-in%C3%A2-vitro-and-in%C3%A2-vivo-involvement-of-oxidative-stress-and-rho-kinase-jnk-signaling-pathways
#2
Xin Liu, Baiyan Sui, Jiao Sun
Silica nanoparticles (SiO2-NPs) has been extensively exploited in biomedical fields and mostly designed to enter the circulatory system, however, few studies focused on the potential adverse effects of SiO2-NPs exposure on the blood-brain barrier (BBB) that serves as a critical barrier between the central nervous system (CNS) and the peripheral circulation. This study attempts to provide an understanding of whether and how SiO2-NPs disrupts the BBB in vitro and in vivo. Through a human BBB model, we found that SiO2-NPs could induce tight junction loss and cytoskeleton arrangement, and increase inflammatory response and the release of vascular endothelial growth factor (VEGF) of brain microvessel endothelial cells (BMECs), which further activates astrocytes to amplify the generation of VEGF and increase the aquaporin-4 expression, and thus causing BBB disruption through a complex immunoregulatory loop between BMECs and astrocytes under SiO2-NPs exposure...
January 4, 2017: Biomaterials
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#3
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28078487/the-role-of-the-nox4-derived-ros-mediated-rhoa-rho-kinase-pathway-in-rat-hypertension-induced-by-chronic-intermittent-hypoxia
#4
Wen Lu, Jing Kang, Ke Hu, Si Tang, Xiufang Zhou, Lifang Xu, Yuanyuan Li, Shuhui Yu
BACKGROUND: Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke...
January 11, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28074433/partial-contribution-of-rho-kinase-inhibition-to-the-bioactivity-of-ganoderma-lingzhi-and-its-isolated-compounds-insights-on-discovery-of-natural-rho-kinase-inhibitors
#5
Yhiya Amen, Qinchang Zhu, Hai-Bang Tran, Mohamed S Afifi, Ahmed F Halim, Ahmed Ashour, Kuniyoshi Shimizu
Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes...
January 10, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28059107/single-cell-time-lapse-analysis-reveals-that-podoplanin-enhances-cell-survival-and-colony-formation-capacity-of-squamous-cell-carcinoma-cells
#6
Tomoyuki Miyashita, Youichi Higuchi, Motohiro Kojima, Atsushi Ochiai, Genichiro Ishii
Tumor initiating cells (TICs) are characterized by high clonal expansion capacity. We previously reported that podoplanin is a TIC-specific marker for the human squamous cell carcinoma cell line A431. The aim of this study is to explore the molecular mechanism underlying the high clonal expansion potential of podoplanin-positive A431cells using Fucci imaging. Single podoplanin-positive cells created large colonies at a significantly higher frequency than single podoplanin-negative cells, whereas no difference was observed between the two types of cells with respect to cell cycle status...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054559/the-rhoa-rock-pathway-ameliorates-adhesion-and-inflammatory-infiltration-induced-by-ages-in-glomerular-endothelial-cells
#7
Jialing Rao, Zengchun Ye, Hua Tang, Cheng Wang, Hui Peng, Weiyan Lai, Yin Li, Wanbing Huang, Tanqi Lou
A recent study demonstrated that advanced glycation end products (AGEs) play a role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular endothelial cells (rGECs) were cultured with AGEs (80 μg/ml) in vitro. The ROCK inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28048944/rho-kinase-inhibitors-a-patent-review-2014-2016
#8
Olivier Defert, Sandro Boland
The Rho-kinases (ROCK), ROCK1 and ROCK2, are potent, widespread biochemical modulators which have been extensively studied. Due to the involvement of ROCKs in multiple biological processes, ROCK inhibitors have pleiotropic actions and may be of relevance for a number of therapeutic applications. The drawback is however that their use might be limited by occurrence of side effects. Areas covered: Since the publication of the latest review in 2014, there have been significant advances in the field of ROCK inhibitors...
January 3, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28043040/rho-kinase-inhibitor-treatment-prevents-pulmonary-inflammation-and-coagulation-in-lipopolysaccharide-induced-lung-injury
#9
Renyu Ding, Dongmei Zhao, Xiaoxia Li, Baoyan Liu, Xiaochun Ma
INTRODUCTION: In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced acute lung injury (ALI) models. METHODS: In the in vivo study, mice were randomized to four different groups: Control, Y-27632 (Y), LPS, and LPS+Y-27632 (LPS+Y)...
December 24, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28039466/elevated-plasma-interleukin-37-playing-an-important-role-in-acute-coronary-syndrome-through-suppression-of-rock-activation
#10
Tengyu Yang, Fang Fang, Yawen Chen, Jing Ma, Zhaowen Xiao, Songfeng Zou, Na Zheng, Dewen Yan, Songyan Liao, Shaoyuan Chen, Hongchen Fang, Chekmen Yu, Jie Liu, Ming Dong
OBJECTIVE: The plasma level of interleukin-37 is elevated in patients with acute coronary syndrome, however, its function during the onset and progress of the disease remains unclear. This study aimed to investigate the clinical significance of IL-37 in acute coronary syndrome and its underlying mechanism. METHODS: 124 patients with acute coronary syndrome and 40 healthy controls were recruited in this study. Plasma interleukin-37 levels were measured in 41 patients with ST elevation myocardial infarction (STEMI), 41 patients with non-STEMI, 42 patients with unstable angina, and 40 controls...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035042/rock1-but-not-rock2-contributes-to-rhoa-signaling-and-nmiia-mediated-contractility-at-the-epithelial-zonula-adherens
#11
Rashmi Priya, Xuan Liang, Jessica L Teo, Kinga Duszyc, Alpha S Yap, Guillermo A Gomez
Rho kinases (ROCK1 and ROCK2) function downstream of the small GTPase RhoA to drive actomyosin cytoskeletal remodeling. It has often been believed that ROCK1 and ROCK2 may be functionally redundant, as they share a highly conserved kinase domain. However, in this study, we report differential functional effects for these ROCKs at the epithelial zonula adherens (ZA). Using specific siRNA, we found that ROCK1 depletion disrupted cadherin organization at the ZA, accompanied by loss of F-actin and NMIIA, whereas ROCK2 knockdown had no significant effect...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28032931/fkbp51-regulates-cell-motility-and-invasion-via-rhoa-signaling
#12
Miho Takaoka, Shun Ito, Yoshio Miki, Akira Nakanishi
FK506 binding protein 51 (FKBP51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP51, i.e., deleted in liver cancer 1 (DLC1) and deleted in liver cancer 2 (DLC2), using immunoprecipitation and mass spectrometry...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28025149/substrate-stiffness-promotes-latent-tgf-%C3%AE-1-activation-in-hepatocellular-carcinoma
#13
Mingshu Pang, Yao Teng, Jianyong Huang, Yuan Yuan, Feng Lin, Chunyang Xiong
Hepatocellular carcinoma (HCC) was usually coupled with increased stiffness of the extracellular matrix (ECM) and elevated level of transforming growth factor-β1 (TGF-β1). However, the mechanism by which substrate rigidity modulated TGF-β1 signaling transduction remained unknown. This paper investigated the molecular mechanism of how matrix stiffness regulating TGF-β1 signaling in HCC cells. By means of stiffness tunable collagen I-coated polyacrylamide (PA) gels, we found that the expressions of β1 integrin, p-FAK (Y397) and p-Smad2 upregulated on stiffer gels as well as the content of TGF-β1 in culture media of HCC cells, which were inhibited by RGD blocking peptides, Y-27632 (ROCK inhibitor) or Blebbistatin (myosin II inhibitor)...
December 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28013338/colon-cancer-cell-derived-12-s-hete-induces-the-retraction-of-cancer-associated-fibroblast-via-mlc2-rho-rock-and-ca-2-signalling
#14
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
December 24, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28002844/activation-of-the-rho-rho-kinase-signaling-pathway-is-involved-in-cell-death-of-corneal-endothelium
#15
Naoki Okumura, Keita Fujii, Takato Kagami, Nakahara Makiko, Miu Kitahara, Shigeru Kinoshita, Noriko Koizumi
Purpose: Rho kinase (ROCK) pathways control fundamental cell functions, making ROCK an important therapeutic target in several pathophysiologic conditions. The purpose of this study was to investigate whether inhibition of ROCK can suppress apoptosis of the corneal endothelium and to determine the role of ROCK signaling in regulating apoptosis. Methods: The effects of inhibitors of ROCK or myosin light chain (MLC) were evaluated in cultured monkey corneal endothelial cells (MCECs) irradiated with ultraviolet (UV) (100 J/m2) to induce apoptosis...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27991930/rho-gtpases-anti-or-pro-neoplastic-targets
#16
REVIEW
I Zandvakili, Y Lin, J C Morris, Y Zheng
Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified that Rac1, RhoA, and some of their effector proteins such as PAK and ROCK, are likely anti-cancer targets for treating K-Ras-driven tumours. Other seemingly contradictory studies have suggested that at least in certain instances inhibition of individual Rho GTPases may paradoxically result in pro-neoplastic effects...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27951595/corneal-endothelial-cell-migration-and-proliferation-enhanced-by-rho-kinase-rock-inhibitors-in-in-vitro-and-in-vivo-models
#17
Landon C Meekins, Noel Rosado-Adames, Rupalatha Maddala, Jiagang J Zhao, Ponugoti V Rao, Natalie A Afshari
Purpose: To explore the role of Rho-associated kinases (ROCK) in corneal physiology and regeneration, and the effects of suppressing its activity in stimulating corneal endothelial cell proliferation and migration in vitro and in vivo. Methods: Immunohistochemistry was performed to detect RhoA and ROCK-1 and ROCK-2 in human corneal tissue. Adult porcine corneal endothelial cells (CECs) were isolated, grown to confluence, and further characterized. Under the treatment of ROCK inhibitors, changes in the cellular distribution profile of ZO-1 and F-actin were examined by immunofluorescence staining...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27930687/mathematical-characterization-of-protein-sequences-using-patterns-as-chemical-group-combinations-of-amino-acids
#18
Jayanta Kumar Das, Provas Das, Korak Kumar Ray, Pabitra Pal Choudhury, Siddhartha Sankar Jana
Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences...
2016: PloS One
https://www.readbyqxmd.com/read/27927737/the-rock-inhibitor-fasudil-prevents-chronic-restraint-stress-induced-depressive-like-behaviors-and-dendritic-spine-loss-in-rat-hippocampus
#19
Gonzalo García-Rojo, Cristóbal Fresno, Natalia Vilches, Gabriela Díaz-Véliz, Sergio Mora, Felipe Aguayo, Aníbal Pacheco, Nicolás Parra-Fiedler, Claudio S Parra, Paulina S Rojas, Macarena Tejos, Esteban Aliaga, Jenny L Fiedler
BACKGROUND: Dendritic arbor simplification and dendritic spine loss in the hippocampus -a limbic structure implicated in mood disorders- are assumed to contribute to symptoms of depression. These morphological changes imply changes in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase (ROCK). We have reported that chronic stress promotes depressive-like behaviors in rats, along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons; changes associated with ROCK activation...
December 7, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27924833/tgf%C3%AE-2-induced-outflow-alterations-in-a-bioengineered-trabecular-meshwork-are-offset-by-a-rho-associated-kinase-inhibitor
#20
Karen Y Torrejon, Ellen L Papke, Justin R Halman, Magnus Bergkvist, John Danias, Susan T Sharfstein, Yubing Xie
Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility...
December 7, 2016: Scientific Reports
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