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Proteomic Analysis of Liver from Human Lipoprotein(a) Transgenic Mice Shows an Oxidative Stress and Lipid Export Response.
- Source :
-
BioMed research international [Biomed Res Int] 2018 Nov 25; Vol. 2018, pp. 4963942. Date of Electronic Publication: 2018 Nov 25 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Background: Mouse models of hypercholesterolaemia have been used to identify arterial proteins involved in atherosclerosis. As the liver is extremely sensitive to dyslipidemia, one might expect major changes in the abundance of liver proteins in these models even before atherosclerosis develops.<br />Methods: Lipid levels were measured and a proteomic approach was used to quantify proteins in the livers of mice with an elevated low-density lipoprotein (LDL) and the presence of lipoprotein(a) [Lp(a)] but no atherosclerosis.<br />Results: The livers of Lp(a) mice showed an increased triglyceride but reduced phospholipid and oxidised lipid content. Two-dimensional gel electrophoresis and mass spectrometry analysis identified 24 liver proteins with significantly increased abundance in Lp(a) mice ( P <0.05). A bioinformatic analysis of the 24 proteins showed the major effect was that of an enhanced antioxidant and lipid efflux response with significant increases in antioxidant (Park7, Gpx1, Prdx6, and Sod1) and lipid metabolism proteins (Fabp4, Acaa2, apoA4, and ApoA1). Interestingly, human liver cells treated with Lp(a) showed significant increases in Gpx1 and Prdx6 but not Sod1 or Park7.<br />Conclusions: The presence of human LDL and Lp(a) in mice promotes an enhanced flux of lipids into the liver which elicits an antioxidant and lipid export response before the onset of atherosclerosis. The antioxidant response can be reproduced in human liver cells treated with Lp(a).
- Subjects :
- Animals
Antioxidants metabolism
Atherosclerosis metabolism
Cell Line, Tumor
Disease Models, Animal
Dyslipidemias metabolism
Female
Hep G2 Cells
Humans
Hypercholesterolemia metabolism
Lipoproteins, LDL metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proteins metabolism
Proteomics methods
Lipid Metabolism physiology
Lipoprotein(a) metabolism
Liver metabolism
Oxidative Stress physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2018
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 30596094
- Full Text :
- https://doi.org/10.1155/2018/4963942