title: Selective oxidative stress and cholesterol metabolism in lipid-metabolizing cell classes: Distinct regulatory roles for pro-oxidants and antioxidants.
abstract: Atherogenesis is associated with macrophage cholesterol and oxidized lipids accumulation and foam cell formation. However, two other major lipid-metabolizing cell classes, namely intestinal and liver cells, are also associated with atherogenesis. This study demonstrates that manipulations of cellular oxidative stress (by fatty acids, glucose, low-density lipoprotein, angiotensin II, polyphenolic antioxidants, or the glutathione/paraoxonase 1 systems) have some similar, but also some different effects on cholesterol metabolism in macrophages (J774A.1) versus intestinal cells (HT-29) versus liver cells (HuH7). Cellular oxidative stress was ≈3.5-folds higher in both intestinal and liver cells versus macrophages. In intestinal cells or liver cells versus macrophages, the cholesterol biosynthesis rate was increased by 9- or 15-fold, respectively. In both macrophages and intestinal cells C-18:1 and C-18:2 but not C-18:0, fatty acids significantly increased oxidative stress, whereas in liver cells oxidative stress was significantly decreased by all three fatty acids. In liver cells, trans C-18:1 versus cis C-18:1, unlike intestinal cells or macrophages, significantly increased cellular oxidative stress and cellular cholesterol biosynthesis rate. Pomegranate juice (PJ), red wine, or their phenolics gallic acids or quercetin significantly reduced cellular oxidation mostly in macrophages. Recombinant PON1 significantly decreased macrophage (but not the other cells) oxidative stress by ≈30%. We conclude that cellular atherogenesis research should look at atherogenicity, not only in macrophages but also in intestinal and liver cells, to advance our understanding of the complicated mechanisms behind atherogenesis. © 2015 BioFactors, 41(4):273-288, 2015.
authors.affiliation: The Lipid Research Laboratory, Technion Rappaport Faculty of Medicine, Haifa, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Rosenblat
authors.affiliation: The Lipid Research Laboratory, Technion Rappaport Faculty of Medicine, Haifa, Israel.
authors.forename: Nina
authors.initials: N
authors.lastname: Volkova
authors.affiliation: The Lipid Research Laboratory, Technion Rappaport Faculty of Medicine, Haifa, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000494:pharmacology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000819:agonists / Q000096:biosynthesis*; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000494:pharmacology; D029561:Lythraceae / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D044242:Trans Fatty Acids / Q000494:pharmacology; D014920:Wine / Q000032:analysis
chemical_list: D000975:Antioxidants; D003374:Coumarins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008077:Lipoproteins, LDL; D010636:Phenols; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D044242:Trans Fatty Acids; D000804:Angiotensin II; D002784:Cholesterol; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: antioxidants; cholesterol biosynthesis; cholesterol efflux; cholesterol influx; intestinal cells; liver cells; macrophages; oxidative stress; paraoxonase