8-11-14-eicosatrienoic-acid and adrenic-acid

Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin

Topics: 8,11,14-Eicosatrienoic Acid; Alleles; Alzheimer Disease; Arachidonic Acid; Case-Control Studies; Chromatography, Gas; Delta-5 Fatty Acid Desaturase; Docosahexaenoic Acids; Erythrocytes; Fatty Acid Desaturases; Fatty Acid Elongases; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Genotype; Humans; Linoleic Acid; Polymorphism, Single Nucleotide; Regression Analysis; Risk Factors; Tunisia

Lipid peroxidation was measured by the thio-barbituric assay for malondialdehyde (MDA). A small amount of MDA was formed when medial cells from guinea pig aorta were grown in tissue culture. The polyunsaturated fatty acids 8,11,14-eicosatrienoic acid, 5,8,11,14-eicosatetraenoic acid, and 7,10,13,16-docosatetraenoic acid generated significant amounts of MDA in a time-dependent manner when they were added to cultures of medial cells and fibroblasts. MDA or its precursor remained within the cell and did not accumulate in the media. Indomethacin enhanced MDA formation from polyunsaturated fatty acid. Alpha-Tocopherol, alpha-tocopherolquinone, and 2,6-di-tert-butyl-4-methylphenol (BHT) inhibited MDA formation when a polyunsaturated fatty acid was incubated with the pro-oxidant cumene hydroperoxide. Menadione had no effect on MDA formation in the cumene hydroperoxide system. Alpha-Tocopherol and alpha-tocopherolquinone inhibited MDA formation when they were added to cells in culture. Menadione had no effect on MDA formation in tissue culture. Anti-oxidant effects which were time-dependent showed that intracellular MDA was generated from a lipid peroxide precursor during the thiobarbituric acid assay. Relative plating efficiency was measured in medial cells and fibroblasts. Alpha-Tocopherolquinone and alpha-tocopherol enhanced the extent of cell proliferation. Alpha-Tocopherolquinone overcame the inhibitory effect of a polyunsaturated fatty acid on the extent of cell proliferation. Menadione was cytotoxic. Thus antioxidant data support the hypothesis that the extent of cell proliferation is controlled in part by lipid peroxidation.

Topics: 5,8,11,14-Eicosatetraynoic Acid; 8,11,14-Eicosatrienoic Acid; Animals; Antioxidants; Cell Division; Cells, Cultured; Erucic Acids; Fatty Acids, Unsaturated; Fibroblasts; Guinea Pigs; Humans; Lipid Peroxides; Male; Malondialdehyde; Muscle, Smooth, Vascular; Vitamin E