title: Relative expression of cholesterol transport-related proteins and inflammation markers through the induction of 7-ketosterol-mediated stress in Caco-2 cells.
abstract: Human diets contain sterol oxidation products that can induce cytotoxic effects, mainly caused by cholesterol oxides. However, phytosterol oxides effects have been less extensively investigated. This study evaluates the production of inflammatory biomarkers (IL-1β, IL-8, IL-10, TNFα) and the influence of gene expression transporters and enzymes related to cholesterol absorption and metabolism (NPC1L1, ABCG5/8, HMGCoA, ACAT) produced by 7-ketosterols (stigmasterol/cholesterol) in Caco-2 cells. These effects were linked to intracellular signaling pathways by using several inhibitors. Results showed 7-ketostigmasterol to have a greater proinflammatory potential than 7-ketocholesterol. In non-pre-treated cells, only efflux transporters were down-regulated by 7-ketosterols, showing a greater influence upon ABCG5 expression. Cell-pre-incubation with bradykinin induced changes in ABCG expression levels after 7-ketostigmasterol-incubation; however, the energetic metabolism inhibition reduced NPC1L1 expression only in 7-ketocholesterol-incubated cells. In non-pre-treated cells, HMG-CoA was up-regulated by both 7-ketosterols. However, exposure to inhibitors down-regulated the expression levels, mainly in 7-ketocholesterol-incubated cells. While ACAT expression values in non-pre-treated cells were unchanged, exposure to inhibitors caused down-regulation of mRNA levels. These results suggest that internalization and excretion of 7-ketostigmasterol is probably influenced by [Ca]i, which also could mediate HMGCoA activity in POPs metabolism. However, energetic metabolism and reducing equivalents exert different influences upon the 7-ketosterol internalization.
authors: Nutrition and Food Chemistry, Faculty of Pharmacy, University of Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors: L
authors: L
authors: Alemany
authors: J M
authors: JM
authors: Laparra
authors: R
authors: R
authors: Barberá
authors: A
authors: A
authors: Alegría
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D018938:Caco-2 Cells; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007653:Ketocholesterols / Q000493:pharmacokinetics*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013265:Stigmasterol / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D015415:Biomarkers; D053583:Interleukin-1beta; D016209:Interleukin-8; D007653:Ketocholesterols; D008074:Lipoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D013265:Stigmasterol; D000101:Acetyl-CoA C-Acetyltransferase; C003001:7-ketocholesterol; D001920:Bradykinin