RhoA/ROCK Regulates Prion Pathogenesis by Controlling Connexin 43 Activity.

Abstract:

:Scrapie infection, which converts cellular prion protein (PrPC) into the pathological and infectious isoform (PrPSc), leads to neuronal cell death, glial cell activation and PrPSc accumulation. Previous studies reported that PrPC regulates RhoA/Rho-associated kinase (ROCK) signaling and that connexin 43 (Cx43) expression is upregulated in in vitro and in vivo prion-infected models. However, whether there is a link between RhoA/ROCK and Cx43 in prion disease pathogenesis is uncertain. Here, we investigated the role of RhoA/ROCK signaling and Cx43 in prion diseases using in vitro and in vivo models. Scrapie infection induced RhoA activation, accompanied by increased phosphorylation of LIM kinase 1/2 (LIMK1/2) at Thr508/Thr505 and cofilin at Ser3 and reduced phosphorylation of RhoA at Ser188 in hippocampal neuronal cells and brains of mice. Scrapie infection-induced RhoA activation also resulted in PrPSc accumulation followed by a reduction in the interaction between RhoA and p190RhoGAP (a GTPase-activating protein). Interestingly, scrapie infection significantly enhanced the interaction between RhoA and Cx43. Moreover, RhoA and Cx43 colocalization was more visible in both the membrane and cytoplasm of scrapie-infected hippocampal neuronal cells than in controls. Finally, RhoA and ROCK inhibition reduced PrPSc accumulation and the RhoA/Cx43 interaction, leading to decreased Cx43 hemichannel activity in scrapie-infected hippocampal neuronal cells. These findings suggest that RhoA/ROCK regulates Cx43 activity, which may have an important role in the pathogenesis of prion disease.

journal_name

Int J Mol Sci

authors

Kim HJ,Kim MJ,Mostafa MN,Park JH,Choi HS,Kim YS,Choi EK

doi

10.3390/ijms21041255

subject

Has Abstract

pub_date

2020-02-13 00:00:00

issue

4

issn

1422-0067

pii

ijms21041255

journal_volume

21

pub_type

杂志文章
  • Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian Macrophages and Modulate Cytokine Production by Activating Multiple Signaling Pathways.

    abstract::The activating leukocyte immunoglobulin-like receptors (LILRAs) play an important role in innate immunity. However, most of the LILRA members have not been characterized in avian species including chickens. The present study is the first attempt at cloning, structural analysis and functional characterization of two LI...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms19092710

    authors: Truong AD,Rengaraj D,Hong Y,Tran HTT,Dang HV,Nguyen VK,Lillehoj HS,Hong YH

    更新日期:2018-09-11 00:00:00

  • Male-Specific Long Noncoding RNA TTTY15 Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4.

    abstract::Gender affects cancer susceptibility. Currently, there are only a few studies on Y chromosome-linked long noncoding RNAs (lncRNAs), and the potential association between lncRNAs and cancers in males has not been fully elucidated. Here, we examined the expression of testis-specific transcript Y-linked 15 (TTTY15) in 37...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20143473

    authors: Lai IL,Chang YS,Chan WL,Lee YT,Yen JC,Yang CA,Hung SY,Chang JG

    更新日期:2019-07-15 00:00:00

  • Structure prediction, molecular dynamics simulation and docking studies of D-specific dehalogenase from Rhizobium sp. RC1.

    abstract::Currently, there is no three-dimensional structure of D-specific dehalogenase (DehD) in the protein database. We modeled DehD using ab initio technique, performed molecular dynamics (MD) simulation and docking of D-2-chloropropionate (D-2CP), D-2-bromopropionate (D-2BP), monochloroacetate (MCA), monobromoacetate (MBA)...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms131215724

    authors: Sudi IY,Wong EL,Joyce-Tan KH,Shamsir MS,Jamaluddin H,Huyop F

    更新日期:2012-11-26 00:00:00

  • The Dark Side of the Force: When the Immune System Is the Fuel of Tumor Onset.

    abstract::Nowadays, it is well accepted that inflammation is a critical player in cancer, being, in most cases, the main character of the process. Different types of tumor arise from sites of infection or chronic inflammation. This non-resolving inflammation is responsible for tumor development at different levels: it promotes ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms22031224

    authors: Digifico E,Balinzo S,Belgiovine C

    更新日期:2021-01-27 00:00:00

  • Metformin Restores Parkin-Mediated Mitophagy, Suppressed by Cytosolic p53.

    abstract::Metformin is known to alleviate hepatosteatosis by inducing 5' adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy. Dysfunctional mitophagy in response to glucolipotoxicities might play an important role in hepatosteatosis. Here, we investigated the mechanism by which metformin induc...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17010122

    authors: Song YM,Lee WK,Lee YH,Kang ES,Cha BS,Lee BW

    更新日期:2016-01-16 00:00:00

  • Application of the SwissDrugDesign Online Resources in Virtual Screening.

    abstract::SwissDrugDesign is an important initiative led by the Molecular Modeling Group of the SIB Swiss Institute of Bioinformatics. This project provides a collection of freely available online tools for computer-aided drug design. Some of these web-based methods, i.e., SwissSimilarity and SwissTargetPrediction, were especia...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20184612

    authors: Daina A,Zoete V

    更新日期:2019-09-18 00:00:00

  • Effect of fiber length on carbon nanotube-induced fibrogenesis.

    abstract::Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding the contribution of physicoc...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms15057444

    authors: Manke A,Luanpitpong S,Dong C,Wang L,He X,Battelli L,Derk R,Stueckle TA,Porter DW,Sager T,Gou H,Dinu CZ,Wu N,Mercer RR,Rojanasakul Y

    更新日期:2014-04-29 00:00:00

  • A Novel Fully Human Agonistic Single Chain Fragment Variable Antibody Targeting Death Receptor 5 with Potent Antitumor Activity In Vitro and In Vivo.

    abstract::Agonistic antibodies, which bind specifically to death receptor 5 (DR5), can trigger apoptosis in tumor cells through the extrinsic pathway. In this present study, we describe the use of a phage display to isolate a novel fully human agonistic single chain fragment variable (scFv) antibody, which targets DR5. After fi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18102064

    authors: Lei G,Xu M,Xu Z,Gu L,Lu C,Bai Z,Wang Y,Zhang Y,Hu H,Jiang Y,Zhao W,Tan S

    更新日期:2017-09-27 00:00:00

  • Chiral Ionic Liquids: Structural Diversity, Properties and Applications in Selected Separation Techniques.

    abstract::Ionic liquids (ILs) are chemical compounds composed of ions with melting points below 100 °C exhibiting a design feature. ILs are commonly used as the so-called green solvents, reagents or highly efficient catalysts in varied chemical processes. The huge application potential of ionic liquids (IL) justifies the growin...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21124253

    authors: Flieger J,Feder-Kubis J,Tatarczak-Michalewska M

    更新日期:2020-06-15 00:00:00

  • Detection of differential levels of proteins in the urine of patients with endometrial cancer: analysis using two-dimensional gel electrophoresis and o-glycan binding lectin.

    abstract::Cancers can cause some proteins to be aberrantly excreted or released in the urine, which can be used as biomarkers. To screen for potential biomarkers for endometrial cancer (ECa), the urinary proteins from patients who were newly diagnosed with early stage ECa and untreated controls were separated using two-dimensio...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms13089489

    authors: Mu AK,Lim BK,Hashim OH,Shuib AS

    更新日期:2012-01-01 00:00:00

  • Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis.

    abstract::Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20081997

    authors: Giuliani KTK,Kassianos AJ,Healy H,Gois PHF

    更新日期:2019-04-23 00:00:00

  • Increase in Efficacy of Checkpoint Inhibition by Cytokine-Induced-Killer Cells as a Combination Immunotherapy for Renal Cancer.

    abstract::Cytokine-induced killer (CIK) cells are heterogeneous, major histocompatibility complex (MHC)-unrestricted T lymphocytes that have acquired the expression of several natural killer (NK) cell surface markers following the addition of interferon gamma (IFN-γ), OKT3 and interleukin-2 (IL-2). Treatment with CIK cells demo...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21093078

    authors: Dehno MN,Li Y,Weiher H,Schmidt-Wolf IGH

    更新日期:2020-04-27 00:00:00

  • Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish.

    abstract::A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance an...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21041464

    authors: Ngoc Hieu BT,Ngoc Anh NT,Audira G,Juniardi S,Liman RAD,Villaflores OB,Lai YH,Chen JR,Liang ST,Huang JC,Hsiao CD

    更新日期:2020-02-21 00:00:00

  • The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.

    abstract::Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the tr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms141019705

    authors: Kumagai K,Kubo M,Imai S,Toyoda F,Maeda T,Okumura N,Matsuura H,Matsusue Y

    更新日期:2013-09-30 00:00:00

  • AKIRIN1: A Potential New Reference Gene in Human Natural Killer Cells and Granulocytes in Sepsis.

    abstract::Timely and reliable distinction of sepsis from non-infectious systemic inflammatory response syndrome (SIRS) supports adequate antimicrobial therapy and saves lives but is clinically challenging. Blood transcriptional profiling promises to deliver insights into the pathomechanisms of SIRS and sepsis and to accelerate ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20092290

    authors: Coulibaly A,Velásquez SY,Sticht C,Figueiredo AS,Himmelhan BS,Schulte J,Sturm T,Centner FS,Schöttler JJ,Thiel M,Lindner HA

    更新日期:2019-05-09 00:00:00

  • Quantitative and chemical fingerprint analysis for the quality evaluation of Isatis indigotica based on ultra-performance liquid chromatography with photodiode array detector combined with chemometric methods.

    abstract::A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms13079035

    authors: Shi YH,Xie ZY,Wang R,Huang SJ,Li YM,Wang ZT

    更新日期:2012-01-01 00:00:00

  • Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.

    abstract::Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatri...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms17040461

    authors: Hernández AF,Menéndez P

    更新日期:2016-03-29 00:00:00

  • Atypical protein phosphatases: emerging players in cellular signaling.

    abstract::It has generally been considered that protein phosphatases have more diverse catalytic domain structures and mechanisms than protein kinases; however, gene annotation efforts following the human genome project appeared to have completed the whole array of protein phosphatases. Ser/Thr phosphatases are divided into thr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms14034596

    authors: Sadatomi D,Tanimura S,Ozaki K,Takeda K

    更新日期:2013-02-26 00:00:00

  • Using a novel microRNA delivery system to inhibit osteoclastogenesis.

    abstract::Previously, we developed a novel microRNA (miRNA) delivery system based on bacteriophage MS2 virus-like particles (MS2 VLPs). In this current study, we used this system to transport miR-146a into human peripheral blood mononuclear cells (PBMCs), and demonstrated the inhibition of osteoclastogenesis in precursors. Two ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms16048337

    authors: Yao Y,Jia T,Pan Y,Gou H,Li Y,Sun Y,Zhang R,Zhang K,Lin G,Xie J,Li J,Wang L

    更新日期:2015-04-14 00:00:00

  • Development of lipid-shell and polymer core nanoparticles with water-soluble salidroside for anti-cancer therapy.

    abstract::Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms15033373

    authors: Fang DL,Chen Y,Xu B,Ren K,He ZY,He LL,Lei Y,Fan CM,Song XR

    更新日期:2014-02-25 00:00:00

  • Terpenes and Terpenoids in Plants: Interactions with Environment and Insects.

    abstract::The interactions of plants with environment and insects are bi-directional and dynamic. Consequently, a myriad of mechanisms has evolved to engage organisms in different types of interactions. These interactions can be mediated by allelochemicals known as volatile organic compounds (VOCs) which include volatile terpen...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21197382

    authors: Boncan DAT,Tsang SSK,Li C,Lee IHT,Lam HM,Chan TF,Hui JHL

    更新日期:2020-10-06 00:00:00

  • Immediate and Late Effects of Early Weaning on Rat Gastric Cell Differentiation.

    abstract::Background: Gastric glands grow and cells reach differentiation at weaning in rats. By considering that early weaning (EW) can affect the timing of development, we aimed to compare molecular and cellular markers of differentiation in pups and adults. Methods: Wistar rats were separated into suckling-control (S) and EW...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21010196

    authors: Teles Silva M,Mesquita da Silva K,Campos Rattes I,Maria Agostini Zonta G,Vasques da Costa A,Galvão Figueredo Costa R,Karen Cordeiro Nogueira L,Ogias D,Gama P

    更新日期:2019-12-27 00:00:00

  • Disease progression mediated by egr-1 associated signaling in response to oxidative stress.

    abstract::When cellular reducing enzymes fail to shield the cell from increased amounts of reactive oxygen species (ROS), oxidative stress arises. The redox state is misbalanced, DNA and proteins are damaged and cellular transcription networks are activated. This condition can lead to the initiation and/or to the progression of...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms131013104

    authors: Pagel JI,Deindl E

    更新日期:2012-10-12 00:00:00

  • The Neosartorya fischeri Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Candida auris Biofilms.

    abstract::Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro acti...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms22020771

    authors: Kovács R,Nagy F,Tóth Z,Forgács L,Tóth L,Váradi G,Tóth GK,Vadászi K,Borman AM,Majoros L,Galgóczy L

    更新日期:2021-01-14 00:00:00

  • Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma.

    abstract::Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and parac...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18010149

    authors: Cadamuro M,Brivio S,Spirli C,Joplin RE,Strazzabosco M,Fabris L

    更新日期:2017-01-13 00:00:00

  • Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles.

    abstract::The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. Lysozyme degrades bacterial cell wall without involving antibiotic resistance and has become a new antibacterial strategy. However, direct use of native, active prot...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21051635

    authors: Wang Y,Li S,Jin M,Han Q,Liu S,Chen X,Han Y

    更新日期:2020-02-27 00:00:00

  • Modulation of SUR1 KATP Channel Subunit Activity in the Peripheral Nervous System Reduces Mechanical Hyperalgesia after Nerve Injury in Mice.

    abstract::The ATP-sensitive K+ channel (KATP) is involved in hypersensitivity during chronic pain and is presumed to be a downstream target of mu opioid receptors. Multiple subtypes of KATP channels exist in the peripheral and central nervous system and their activity may be inversely correlated to chronic pain phenotypes in ro...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20092251

    authors: Luu W,Bjork J,Salo E,Entenmann N,Jurgenson T,Fisher C,Klein AH

    更新日期:2019-05-07 00:00:00

  • Sunflower-based feedstocks in nonfood applications: Perspectives from olefin metathesis.

    abstract::Sunflower (Helianthus annuus L.) oil remains under-utilised albeit one of the major seed oils produced world-wide. Moreover, the high oleic sunflower varieties make the oil attractive for applications requiring high temperature processes and those targeting the C=C double bond functionality. Herein an overview of the ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms9081393

    authors: Marvey BB

    更新日期:2008-08-01 00:00:00

  • Influence of Cationic meso-Substituted Porphyrins on the Antimicrobial Photodynamic Efficacy and Cell Membrane Interaction in Escherichia coli.

    abstract::Photodynamic inactivation (PDI) is a non-antibiotic option for the treatment of infectious diseases. Although Gram-positive bacteria have been shown to be highly susceptible to PDI, the inactivation of Gram-negative bacteria has been more challenging due to the impermeability properties of the outer membrane. In the p...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20010134

    authors: Hurst AN,Scarbrough B,Saleh R,Hovey J,Ari F,Goyal S,Chi RJ,Troutman JM,Vivero-Escoto JL

    更新日期:2019-01-01 00:00:00

  • Hydroxyl Radical-Suppressing Mechanism and Efficiency of Melanin-Mimetic Nanoparticles.

    abstract::Harnessing melanins to scavenge free radicals in vivo may yield treatment methods for inflammatory disorders. Furthermore, elucidation of the mechanism underlying melanin-mediated suppression of free radicals, which is yet unclear, is warranted. Herein, we chemically synthesized melanin-mimetic nanoparticles (MeNPs) a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms19082309

    authors: Hayashi K,Tokuda A,Sakamoto W

    更新日期:2018-08-07 00:00:00