title: Elaidate, an 18-carbon trans-monoenoic fatty acid, but not physiological fatty acids increases intracellular Zn(2+) in human macrophages.
abstract: Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 min treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 h. To determine longer term effects of trans fatty acids, we compared mRNA expression profiles of (trans) elaidate to (cis) oleate, 30 μM, at 44 h in human macrophages. We found that elaidate changed Zn(2+) -homeostasis gene mRNAs markedly. This might be important because Zn(2+) is a major regulator of macrophage activity. Messenger RNAs of seven Zn(2+) -binding metallothioneins decreased 2-4-fold; the zinc importer SLC39A10 increased twofold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn(2+) -homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 h. Further, intracellular Zn(2+) was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl) amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 h, only cells treated with elaidate had increased Zn(2+) . The durable effect of elaidate on Zn(2+) activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261.
authors.forename: Janelle R
authors.initials: JR
authors.lastname: Zacherl
authors.forename: Irina
authors.initials: I
authors.lastname: Tourkova
authors.forename: Claudette M
authors.initials: CM
authors.lastname: St Croix
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Octavia M
authors.initials: OM
authors.lastname: Peck Palmer
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Mihalik
authors.forename: Harry C
authors.initials: HC
authors.lastname: Blair
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics*; D019301:Oleic Acid / Q000494:pharmacology*; D009829:Oleic Acids; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D005227:Fatty Acids; D009829:Oleic Acids; C519886:SLC39A10 protein, human; D019301:Oleic Acid; C011459:elaidic acid; D008668:Metallothionein; D015032:Zinc
keywords: ATHEROSCLEROSIS; INTRACELLULAR ZINC; MACROPHAGE METABOLISM; TRANS FAT