Exposure to atheroma-relevant 7-oxysterols causes proteomic alterations in cell death, cellular longevity, and lipid metabolism in THP-1 macrophages

The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic le...

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Bibliographic Details
Published in:PloS one 2017-03, Vol.12 (3), p.e0174475-e0174475
Main Authors: Ward, Liam J, Ljunggren, Stefan A, Karlsson, Helen, Li, Wei, Yuan, Xi-Ming
Format: Article
Language:English
Subjects:
Analysis
Apoptosis
Apoptosis - drug effects
Atherosclerosis
Atherosclerotic plaque
Autophagy - drug effects
Biology and Life Sciences
Blotting, Western
Cell death
Cell Death - drug effects
Cell Line, Tumor
Cell Survival - drug effects
Cholesterol
Diagnosis
Electrophoresis
Electrophoresis, Gel, Two-Dimensional
Environmental health
Experiments
Exposure
Foams
Gene expression
Gynecology
Humans
Hydroxycholesterols - pharmacology
Inflammation
Ketocholesterols - pharmacology
Lipid metabolism
Lipid Metabolism - drug effects
Lipids
Longevity
Macrophages
Macrophages - drug effects
Macrophages - metabolism
Mass spectrometry
Medicine
Medicine and Health Sciences
Metabolism
Metabolites
Obstetrics
Oxidative stress
Oxysterols - metabolism
Oxysterols - pharmacology
Physiological aspects
Physiology
Plaque, Atherosclerotic - metabolism
Proteins
Proteome - metabolism
Proteomics
Proteomics - methods
Scavenger receptors
Signal transduction
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectroscopy
Tandem Mass Spectrometry
Time Factors
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Summary:The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome. Human THP-1 macrophages were exposed to an atheroma-relevant mixture of 7β-hydroxycholesterol and 7-ketocholesterol. Two-dimensional gel electrophoresis and mass spectrometry techniques were used to analyse the alterations in macrophage proteome, which resulted in the identification of 19 proteins with significant differential expression upon oxysterol loading; 8 increased and 11 decreased. The expression patterns of 11 out of 19 identified significant proteins were further confirmed by tandem-mass spectrometry, including further validation of increased histone deacetylase 2 and macrophage scavenger receptor types I and II expressions by western blot analysis. Identified proteins with differential expression in the cell model have been associated with i) signalling imbalance in cell death and cellular longevity; ii) lipid uptake and metabolism in foam cells; and iii) inflammatory proteins. The presented findings highlight a new proteomic platform for further studies into the functional roles of macrophages in atherosclerosis, and present a cell model for future studies to modulate the macrophage proteome by potential anti-atherosclerotic agents.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0174475