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J Proteomics. 2018 Jun 15;181:118-130. doi: 10.1016/j.jprot.2018.04.008. Epub 2018 Apr 12.

Myristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells.

Author information

1
Department of Biotechnology, Proteomics and Mass Spectrometry Laboratory, University of Verona, Strada le Grazie 15, Verona, Italy.
2
Research Unit of Functional Proteomics and Metabolic Pathways, Institute of Pathology, Medical University of Graz, Graz, Austria; Omics Center Graz, BioTechMed-Graz, Graz, Austria.
3
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
4
Research Unit of Functional Proteomics and Metabolic Pathways, Institute of Pathology, Medical University of Graz, Graz, Austria; Omics Center Graz, BioTechMed-Graz, Graz, Austria; Institute of Computational Biotechnology, Graz University of Technology, Graz, Austria.
5
Department of Medicine, Unit of Internal Medicine, University of Verona, P.le L.A. Scuro 10, Verona, Italy.
6
Omics Center Graz, BioTechMed-Graz, Graz, Austria; Institute of Computational Biotechnology, Graz University of Technology, Graz, Austria.
7
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria.
8
Research Unit of Functional Proteomics and Metabolic Pathways, Institute of Pathology, Medical University of Graz, Graz, Austria; Omics Center Graz, BioTechMed-Graz, Graz, Austria; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria.
9
Research Unit of Functional Proteomics and Metabolic Pathways, Institute of Pathology, Medical University of Graz, Graz, Austria; Omics Center Graz, BioTechMed-Graz, Graz, Austria; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address: ruth.birner-gruenberger@medunigraz.at.
10
Department of Biotechnology, Proteomics and Mass Spectrometry Laboratory, University of Verona, Strada le Grazie 15, Verona, Italy. Electronic address: daniela.cecconi@univr.it.

Abstract

Myristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.

BIOLOGICAL SIGNIFICANCE:

Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.

KEYWORDS:

HepG2 cells; Myristic acid; Primary murine hepatocytes; Proteome; Secretome

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