Differential regulation of protein expression in response to polyunsaturated fatty acids in the liver of apoE-knockout mice and in HepG2 cells
Journal
Journal of Biomedical Science
Journal Volume
22
Journal Issue
1
Date Issued
2015
Author(s)
Abstract
Background: Polyunsaturated fatty acids (PUFAs) are nutrients necessary for life. The liver is the essential metabolic center, which aids in maintaining health via diverse biological actions. In the present work, a proteomics study was conducted with an aim to provide new insights into PUFA-regulated hepatic protein expression in apoE-knockout mice. Additionally, we investigated how n-3 PUFAs influence cytokine-challenge by using HepG2 cells as a model. Results: Through the proteomic analysis using 2-dimensional electrophoresis and mass spectrometry, we found that 28, 23, 14, and 28 hepatic proteins were up-regulated at least a two-fold difference in intensity compared with the control group in mice treated with the docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and linoleic acid, respectively. In contrast, 12 hepatic proteins were down-regulated with a ratio value of less than 0.5 compared to their control counterparts by these four fatty acids. All of the altered proteins were then sorted according to their biochemical properties related to metabolism, redox stress/inflammation, enzymatic reactions, and miscellaneous functions. The results provide evidence that PUFAs may act as either pro-inflammatory or anti-inflammatory agents. Cytokine-challenged HepG2 cells were used to reveal the anti-inflammatory function of n-3 PUFAs. The results showed that interleukin (IL)-1β combined with IL-6 induced C-reactive protein (CRP) mRNA expression and its protein secretion by HepG2 cells. The CRP promoter activity was significantly increased in the IL-6-treated cells, whereas IL-1β alone had no effect. However, IL-1β and IL-6 acted synergistically to further enhance CRP promoter activities. Furthermore, n-3 PUFAs inhibited nuclear factor-κB (NF-κB) activation and the phosphorylation of the nuclear signal transducer and activator of transcription 3 (STAT3) during cytokine-induced CRP production. Conclusion: This study indicates that PUFAs induced changes in the hepatic protein profile in vivo. Furthermore, n-3 PUFAs exert their anti-inflammatory properties through differential molecular mechanisms in hepatic cells. These results provide novel information regarding the roles of PUFAs in the liver at the tissue and cellular levels. ? 2015 Huang et al.; licensee BioMed Central.
Subjects
C-reactive protein (CRP); Inflammation; Nuclear factor-κB (NF-κB) pathway; Polyunsaturated fatty acids (PUFAs); Proteomics
SDGs
Other Subjects
aldehyde dehydrogenase; alpha enolase; apolipoprotein E; arachidonic acid; C reactive protein; chaperonin 60; cyclophilin A; docosahexaenoic acid; fumarylacetoacetase; glutathione peroxidase 1; glutathione transferase M1; I kappa B; icosapentaenoic acid; interferon regulatory factor; interleukin 1beta; interleukin 6; isocitrate dehydrogenase; linoleic acid; liver protein; malate dehydrogenase; mitogen activated protein kinase 10; peroxiredoxin 4; phosphoglucomutase; polyunsaturated fatty acid; proteome; pyruvate carboxylase; STAT3 protein; sterol regulatory element binding protein 1; succinyl coenzyme A synthetase; vitamin D binding protein; C reactive protein; messenger RNA; unsaturated fatty acid; animal experiment; animal model; animal tissue; Article; comparative study; controlled study; down regulation; gene control; gene expression; knockout mouse; lipid liver level; liver cell carcinoma; mass spectrometry; mouse; nonhuman; priority journal; protein expression; protein function; protein phosphorylation; protein secretion; proteomics; quantitative analysis; randomized controlled trial; real time polymerase chain reaction; redox stress; reverse transcription polymerase chain reaction; signal transduction; transient transfection; two dimensional gel electrophoresis; upregulation; Western blotting; animal; gene expression regulation; Hep-G2 cell line; human; liver; male; metabolism; signal transduction; Mus; Animals; C-Reactive Protein; Fatty Acids, Unsaturated; Gene Expression Regulation; Hep G2 Cells; Humans; Liver; Male; Mice; Mice, Knockout; RNA, Messenger; Signal Transduction
Type
journal article