Author, as appears in the article.: Saavedra P; Girona J; Bosquet A; Guaita S; Canela N; Aragonès G; Heras M; Masana L

Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques

URV's Author/s: ARAGONÈS BARGALLÓ, GEMMA / BOSQUET AGUDO, ALBA / Girona Tell, Josefa / GUAITA ESTERUELAS, SANDRA / HERAS IBAÑEZ, MERCEDES / Masana Marín, Luis / SAAVEDRA GARCIA, PAULA

Keywords: 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

Abstract: © 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.

Thematic Areas: 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

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 01674889

Author's mail: josefa.girona@urv.cat luis.masana@urv.cat josefa.girona@urv.cat

Author identifier: 0000-0002-6267-8779 0000-0002-0789-4954 0000-0002-6267-8779

Record's date: 2023-02-26

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S0167488915002955?via%3Dihub

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Biochimica Et Biophysica Acta-Molecular Cell Research. 1853 (11): 2966-2974

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

Article's DOI: 10.1016/j.bbamcr.2015.09.002

Entity: Universitat Rovira i Virgili

Journal publication year: 2015

Publication Type: Journal Publications