title: p38 MAPK protects human monocytes from postprandial triglyceride-rich lipoprotein-induced toxicity.
abstract: Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids.
authors.affiliation: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, The Spanish National Research Council, Seville, Spain. serglom@ig.csic.es
authors.forename: Sergio
authors.initials: S
authors.lastname: Lopez
authors.forename: Sara
authors.initials: S
authors.lastname: Jaramillo
authors.forename: Lourdes M
authors.initials: LM
authors.lastname: Varela
authors.forename: Almudena
authors.initials: A
authors.lastname: Ortega
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bermudez
authors.forename: Rocio
authors.initials: R
authors.lastname: Abia
authors.forename: Francisco J G
authors.initials: FJ
authors.lastname: Muriana
mesh_terms: D002079:Butter; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D005227:Fatty Acids / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D000069463:Olive Oil; D010766:Phosphorylation; D010938:Plant Oils / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019518:Postprandial Period; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000074242:Sunflower Oil; D014280:Triglycerides / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D008074:Lipoproteins; D000069463:Olive Oil; D010938:Plant Oils; D017382:Reactive Oxygen Species; D000074242:Sunflower Oil; D014280:Triglycerides; C030087:lipoprotein triglyceride; D002079:Butter; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3