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https://www.readbyqxmd.com/read/28054559/the-rhoa-rock-pathway-ameliorates-adhesion-and-inflammatory-infiltration-induced-by-ages-in-glomerular-endothelial-cells
#1
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
#2
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/28035042/rock1-but-not-rock2-contributes-to-rhoa-signaling-and-nmiia-mediated-contractility-at-the-epithelial-zonula-adherens
#3
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/28031255/rock-signaling-promotes-collagen-remodeling-to-facilitate-invasive-pancreatic-ductal-adenocarcinoma-tumor-cell-growth
#4
Nicola Rath, Jennifer P Morton, Linda Julian, Lena Helbig, Shereen Kadir, Ewan J McGhee, Kurt I Anderson, Gabriela Kalna, Margaret Mullin, Andreia V Pinho, Ilse Rooman, Michael S Samuel, Michael F Olson
Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a Kras(G12D)/p53(R172H) mouse PDAC model, was associated with reduced survival. Conditional ROCK1 or ROCK2 activation promoted invasive growth of mouse PDAC cells into three-dimensional collagen matrices by increasing matrix remodeling activities...
December 28, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27917311/rock-inhibition-promotes-attachment-proliferation-and-wound-closure-in-human-embryonic-stem-cell-derived-retinal-pigmented-epithelium
#5
Roxanne H Croze, William J Thi, Dennis O Clegg
PURPOSE: Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD...
November 2016: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/27890541/the-expression-of-plasticity-related-genes-in-an-acute-model-of-stress-is-modulated-by-chronic-desipramine-in-a-time-dependent-manner-within-medial-prefrontal-cortex
#6
Nicoletta Nava, Giulia Treccani, Heidi Kaastrup Müller, Maurizio Popoli, Gregers Wegener, Betina Elfving
It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI)...
November 24, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27885213/a-fret-biosensor-for-rock-based-on-a-consensus-substrate-sequence-identified-by-kiss-technology
#7
Chunjie Li, Ayako Imanishi, Naoki Komatsu, Kenta Terai, Mutsuki Amano, Kozo Kaibuchi, Michiyuki Matsuda
Genetically-encoded biosensors based on Förster/fluorescence resonance energy transfer (FRET) are versatile tools for studying the spatio-temporal regulation of signaling molecules within not only the cells but also tissues. Perhaps the hardest task in the development of a FRET biosensor for protein kinases is to identify the kinase-specific substrate peptide to be used in the FRET biosensor. To solve this problem, we took advantage of kinase-interacting substrate screening (KISS) technology, which deduces a consensus substrate sequence for the protein kinase of interest...
November 23, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27881000/microrna-584-3p-reduces-the-vasculogenic-mimicry-of-human-glioma-cells-by-regulating-hypoxia-induced-rock1-dependent-stress-fiber-formation
#8
S Xu, J Zhang, H Xue, X Guo, X Han, T Li, X Guo, X Gao, Q Liu, G Li
We report in this study that microRNA-584-3p (miR-584-3p) is related to the vasculogenic mimicry (VM) of human glioma cells. Unsurprisingly, the postoperative survival time was significantly prolonged in those glioma patients without VM phenomena compared with those with positive VM. miR-584-3p may function as a potent tumor suppressor by inhibiting VM of malignant glioma. However, the molecular mechanisms underlying these properties remain poorly understood. Our preliminary mechanistic studies revealed that miR-584-3p suppressed the VM by disturbing hypoxia-induced stress fiber formation and migration of glioma cells...
November 24, 2016: Neoplasma
https://www.readbyqxmd.com/read/27877086/ginsenoside-rg1-protects-against-oxidative-stress-induced-neuronal-apoptosis-through-myosin-iia-actin-related-cytoskeletal-reorganization
#9
Yan Wang, Qian Liu, Yingqiong Xu, Yuanyuan Zhang, Yanni Lv, Yisha Tan, Nan Jiang, Guosheng Cao, Xiaonan Ma, Jingrong Wang, Zhengyu Cao, Boyang Yu, Junping Kou
Oxidative stress-induced cytoskeletal dysfunction of neurons has been implicated as a crucial cause of cell apoptosis or death in the central nervous system (CNS) diseases, such as neurodegenerative and psychiatric diseases. The application of neuroprotectants rescuing the neurons from cytoskeletal damage and apoptosis can be a potential treatment for these CNS diseases. Ginsenoside Rg1 (Rg1), one of the major active components of ginseng, has been reported possessing notable neuroprotective activities. However, there is rare report about its effect on cytoskeleton and its undergoing mechanism...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27853422/rock1-is-associated-with-alzheimer-s-disease-specific-plaques-as-well-as-enhances-autophagosome-formation-but-not-autophagic-a%C3%AE-clearance
#10
Yong-Bo Hu, Yang Zou, Yue Huang, Yong-Fang Zhang, Guinevere F Lourenco, Sheng-Di Chen, Glenda M Halliday, Gang Wang, Ru-Jing Ren
Alzheimer's disease (AD) is the most prevalent form of late-life dementia in the population, characterized by amyloid plaque formation and increased tau deposition, which is modulated by Rho-associated coiled-coil kinase 1 (ROCK1). In this study, we further analyze whether ROCK1 regulates the metabolism of amyloid precursor protein (APP). We show that ROCK1 is colocalized with mature amyloid-β (Aβ) plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aβ in a cell model of AD (confirmed by increased ROCK1 and decreased Beclin 1 protein levels, with neuronal autophagosome accumulation in prefrontal cortex of AD APP/PS1 mouse model)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27852062/disrupted-in-schizophrenia-1-disc1-inhibits-glioblastoma-development-by-regulating-mitochondria-dynamics
#11
Xingchun Gao, Yajing Mi, Na Guo, Zhifang Hu, Fengrui Hu, Dou Liu, Lei Gao, Xingchun Gou, Weilin Jin
Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27824338/rock-signalling-induced-gene-expression-changes-in-mouse-pancreatic-ductal-adenocarcinoma-cells
#12
Nicola Rath, Gabriela Kalna, William Clark, Michael F Olson
The RhoA and RhoC GTPases act via the ROCK1 and ROCK2 kinases to promote actomyosin contraction, resulting in directly induced changes in cytoskeleton structures and altered gene transcription via several possible indirect routes. Elevated activation of the Rho/ROCK pathway has been reported in several diseases and pathological conditions, including disorders of the central nervous system, cardiovascular dysfunctions and cancer. To determine how increased ROCK signalling affected gene expression in pancreatic ductal adenocarcinoma (PDAC) cells, we transduced mouse PDAC cell lines with retroviral constructs encoding fusion proteins that enable conditional activation of ROCK1 or ROCK2, and subsequently performed RNA sequencing (RNA-Seq) using the Illumina NextSeq 500 platform...
November 8, 2016: Scientific Data
https://www.readbyqxmd.com/read/27798869/ursolic-acid-suppresses-hepatitis-b-virus-x-protein-mediated-autophagy-and-chemotherapeutic-drug-resistance
#13
Ching-Dong Chang, Ping-Yuan Lin, Jue-Liang Hsu, Wen-Ling Shih
Hepatitis B virus X (HBx) protein is a multifunctional oncoprotein that affects diverse cell activities via regulation of various host cell signaling pathways. The current investigation demonstrated that ursolic acid (UA), a pentacyclic triterpenoid, protected hepatoma cells and reduced HBx-mediated autophagy through modulation of Ras homolog gene family member A (RhoA). Low-level ectopic HBx expression in Huh7 cells induced more significant autophagosome formation than high-level HBx expression. HBx activated beclin-1 promoter and enhanced the beclin-1 protein expression under low HBx expression...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27795708/broad-spectrum-anticancer-activity-of-myo-inositol-and-inositol-hexakisphosphate
#14
REVIEW
Mariano Bizzarri, Simona Dinicola, Arturo Bevilacqua, Alessandra Cucina
Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27791202/fasudil-an-inhibitor-of-rho-associated-coiled-coil-kinase-improves-cognitive-impairments-induced-by-smoke-exposure
#15
Deng Xueyang, Ma Zhanqiang, Ma Chunhua, Hao Kun
The current study was designed to investigate the pathological changes in brain induced by smoke exposure, and explore whether fasudil could alleviate these impairments.Adult C57BL/6 mice were exposed to tobacco smoking for four months, and fasudil was treated from the third months. To investigate lung injuries, the immunohistochemistry of lung tissue, immune cell infiltrations, cytokine productions in bronchoalveolar lavage (BAL) fluid, and seurm inflammatory cytokines were evaluated. To investigate cognitive impairments, Morris water maze test, hippocampal inflammatory cytokines and Rho associated signaling pathways were evaluated...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27775859/tissue-selective-expression-of-a-conditionally-active-rock2-estrogen-receptor-fusion-protein
#16
Michael S Samuel, Nicola Rath, Siti F Masre, Sarah T Boyle, David A Greenhalgh, Marina Kochetkova, Sheila Bryson, David Stevenson, Michael F Olson
The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER)...
December 2016: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27771900/rhoa-rho-kinase-mediates-neuronal-death-through-regulating-cpla2-activation
#17
Xiangbing Wu, Chandler L Walker, Qingbo Lu, Wei Wu, Daniel B Eddelman, Jonathan M Parish, Xiao-Ming Xu
Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A2 (cPLA2), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27764233/escrt-i-protein-tsg101-plays-a-role-in-the-post-macropinocytic-trafficking-and-infection-of-endothelial-cells-by-kaposi-s-sarcoma-associated-herpesvirus
#18
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27763717/additive-effects-of-the-rho-kinase-inhibitor-y-27632-and-vardenafil-on-relaxation-of-the-corpus-cavernosum-tissue-of-patients-with-erectile-dysfunction-and-clinical-phosphodiesterase-type-5-inhibitor-failure
#19
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk J M K De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR])...
October 20, 2016: BJU International
https://www.readbyqxmd.com/read/27754222/os-32-07-levorotatory-amlodipine-plus-fluvastatin-confer-additive-effects-on-retarding-endothelium-mesenchymal-transition-through-suppressing-rock1-expression
#20
Anping Cai, Yingqing Feng, Yingling Zhou, Jiyan Chen
OBJECTIVE: To investigate the effects and mechanisms of levorotatory (L)-amlodipine combined fluvastatin treatment on endothelium-mesenchymal transition (EndMT), a process related to hypertension development. DESIGN AND METHOD: Human umbilical vein endothelial cells (HUVECs) were used and divided to six groups based on different therapeutic strategies as follows: Blank Control, angiotensin-II (Ang-II), Ang-II+ rho-associated kinase (ROCK) inhibitor, Ang-II+ L-amlodipine, Ang-II+ fluvastatin, and Ang-II +L-amlodipine + fluvastatin groups...
September 2016: Journal of Hypertension
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