Articles producció científica> Medicina i Cirurgia

New insights into circulating FABP4: Interaction with cytokeratin 1 on endothelial cell membranes

  • Dades identificatives

    Identificador: imarina:6388336
    Autors:
    Saavedra PGirona JBosquet AGuaita SCanela NAragonès GHeras MMasana L
    Resum:
    © 2015 Published by Elsevier B.V. Fatty acid-binding protein 4 (FABP4) is an adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation. Increased levels of circulating FABP4 have been detected in individuals with cardiovascular risk factors. Recent studies have demonstrated that FABP4 has a direct effect on peripheral tissues, specifically promoting vascular dysfunction; however, its mechanismof action is unknown. The objective of this work was to assess the specific interactions between exogenous FABP4 and the plasma membranes of endothelial cells. Immunofluorescence assays showed that exogenous FABP4 localized along the plasma membranes of human umbilical vein endothelial cells (HUVECs), interacting specificallywith plasma membrane proteins. Anti-FABP4 immunoblotting revealed two covalent protein complexes containing FABP4 and its putative receptor; these complexes were approximately 108 kDa and 77 kDa in size. Proteomics and mass spectrometry experiments revealed that cytokeratin 1 (CK1)was the FABP4-binding protein. An anti-CK1 immunoblot confirmed the presence of CK1. FABP4-CK1 complexes were also detected in HAECs, HCASMCs, HepG2 cells and THP-1 cells. Pharmacological FABP4 inhibition by BMS309403 results in a slight decrease in the formation of these complexes, indicating that fatty acids may play a role in FABP4 functionality. In addition, we demonstrated that exogenous FABP4 crosses the plasma membrane to enter the cytoplasm and nucleus in HUVECs. These findings indicate that exogenous FABP4 interacts with plasma membrane proteins, specifically CK1. These data contribute to our current knowledge regarding the mechanismof action of circulating FABP4.
  • Altres:

    Autor segons l'article: Saavedra P; Girona J; Bosquet A; Guaita S; Canela N; Aragonès G; Heras M; Masana L
    Departament: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    Autor/s de la URV: ARAGONÈS BARGALLÓ, GEMMA / BOSQUET AGUDO, ALBA / Girona Tell, Josefa / GUAITA ESTERUELAS, SANDRA / HERAS IBAÑEZ, MERCEDES / Masana Marín, Luis / SAAVEDRA GARCIA, PAULA
    Paraules clau: Plasminogen-activator receptor Plasma fatty-acid-binding-protein-4 Oxidative stress Obesity Mice Metabolic syndrome Insulin-resistance Fabp4 inhibition Fabp4 Endothelial cell Cytokeratin 1 Cell surface receptor Carotid atherosclerosis Biomarker Acid-binding protein fabp4 endothelial cell cytokeratin 1 cell surface receptor
    Resum: © 2015 Published by Elsevier B.V. Fatty acid-binding protein 4 (FABP4) is an adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation. Increased levels of circulating FABP4 have been detected in individuals with cardiovascular risk factors. Recent studies have demonstrated that FABP4 has a direct effect on peripheral tissues, specifically promoting vascular dysfunction; however, its mechanismof action is unknown. The objective of this work was to assess the specific interactions between exogenous FABP4 and the plasma membranes of endothelial cells. Immunofluorescence assays showed that exogenous FABP4 localized along the plasma membranes of human umbilical vein endothelial cells (HUVECs), interacting specificallywith plasma membrane proteins. Anti-FABP4 immunoblotting revealed two covalent protein complexes containing FABP4 and its putative receptor; these complexes were approximately 108 kDa and 77 kDa in size. Proteomics and mass spectrometry experiments revealed that cytokeratin 1 (CK1)was the FABP4-binding protein. An anti-CK1 immunoblot confirmed the presence of CK1. FABP4-CK1 complexes were also detected in HAECs, HCASMCs, HepG2 cells and THP-1 cells. Pharmacological FABP4 inhibition by BMS309403 results in a slight decrease in the formation of these complexes, indicating that fatty acids may play a role in FABP4 functionality. In addition, we demonstrated that exogenous FABP4 crosses the plasma membrane to enter the cytoplasm and nucleus in HUVECs. These findings indicate that exogenous FABP4 interacts with plasma membrane proteins, specifically CK1. These data contribute to our current knowledge regarding the mechanismof action of circulating FABP4.
    Àrees temàtiques: Química Odontología Molecular biology Medicina i Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Cell biology Biophysics Biochemistry & molecular biology Astronomia / física
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 01674889
    Adreça de correu electrònic de l'autor: josefa.girona@urv.cat josefa.girona@urv.cat luis.masana@urv.cat
    Identificador de l'autor: 0000-0002-6267-8779 0000-0002-6267-8779 0000-0002-0789-4954
    Data d'alta del registre: 2024-09-07
    Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
    Enllaç font original: https://www.sciencedirect.com/science/article/pii/S0167488915002955?via%3Dihub
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Biochimica Et Biophysica Acta-Molecular Cell Research. 1853 (11): 2966-2974
    Referència de l'ítem segons les normes APA: Saavedra P; Girona J; Bosquet A; Guaita S; Canela N; Aragonès G; Heras M; Masana L (2015). New insights into circulating FABP4: Interaction with cytokeratin 1 on endothelial cell membranes. Biochimica Et Biophysica Acta-Molecular Cell Research, 1853(11), 2966-2974. DOI: 10.1016/j.bbamcr.2015.09.002
    DOI de l'article: 10.1016/j.bbamcr.2015.09.002
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2015
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry & Molecular Biology,Biophysics,Cell Biology,Molecular Biology
    Plasminogen-activator receptor
    Plasma fatty-acid-binding-protein-4
    Oxidative stress
    Obesity
    Mice
    Metabolic syndrome
    Insulin-resistance
    Fabp4 inhibition
    Fabp4
    Endothelial cell
    Cytokeratin 1
    Cell surface receptor
    Carotid atherosclerosis
    Biomarker
    Acid-binding protein
    fabp4
    endothelial cell
    cytokeratin 1
    cell surface receptor
    Química
    Odontología
    Molecular biology
    Medicina i
    Farmacia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Cell biology
    Biophysics
    Biochemistry & molecular biology
    Astronomia / física
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