Dataset Information

Intestinal and Hepatic Uptake of Dietary Peroxidized Lipids and Their Decomposition Products, and Their Subsequent Effects on Apolipoprotein A1 and Paraoxonase1.

ABSTRACT: Both pro- and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary peroxidized lipids and their decomposition products. This study sought to determine the metabolic fate and physiological ramifications of 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 13-HODE (13-hydroxyoctadecadienoic acid) supplementation in intestinal and hepatic cell lines, as well as any effects resulting from 13-HPODE or 13-HODE degradation products. In the presence of Caco-2 cells, 13-HPODE was rapidly reduced to 13-HODE. Upon entering the cell, 13-HODE appears to undergo decomposition, followed by esterification. Moreover, 13-HPODE undergoes autodecomposition to produce aldehydes such as 9-oxononanoic acid (9-ONA). Results indicate that 9-ONA was oxidized to azelaic acid (AzA) rapidly in cell culture media, but AzA was poorly absorbed by intestinal cells and remained detectable in cell culture media for up to 18 h. An increased apolipoprotein A1 (ApoA1) secretion was observed in Caco-2 cells in the presence of 13-HPODE, 9-ONA, and AzA, whereas such induction was not observed in HepG2 cells. However, 13-HPODE treatments suppressed paraoxonase 1 (PON1) activity, suggesting the induction of ApoA1 secretion by 13-HPODE may not represent functional high-density lipoprotein (HDL) capable of reducing oxidative stress. Alternatively, AzA induced both ApoA1 secretion and PON1 activity while suppressing ApoB secretion in differentiated Caco-2 cells but not in HepG2. These results suggest oxidation of 9-ONA to AzA might be an important phenomenon, resulting in the accumulation of potentially beneficial dietary peroxidized lipid-derived aldehydes.

SUBMITTER: Jiang X

PROVIDER: S-EPMC8389297 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Reactive electrophiles generated by lipid peroxidation are thought to contribute to cardiovascular disease and other oxidative stress-related pathologies by covalently modifying proteins and affecting critical protein functions. The difficulty of capturing and analyzing the relatively small fraction of modified proteins complicates identification of the protein targets of lipid electrophiles. We recently synthesized a biotin-modified linoleoylglycerylphosphatidylcholine probe called PLPBSO ( Tallman et al. Chem. Res. Toxicol. 2007, 20, 227-234 ), which forms typical linoleate oxidation products and covalent adducts with model peptides and proteins. Supplementation of human plasma with PLPBSO followed by free radical oxidation resulted in covalent adduction of PLPBSO to plasma proteins, which were isolated with streptavidin and identified by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Among the most highly modified proteins was apolipoprotein A1 (ApoA1), which is the core component of high density lipoprotein (HDL). ApoA1 phospholipid adduct sites were mapped by LC-MS-MS of tryptic peptides following mild base hydrolysis to release esterified phospholipid adducts. Several carboxylated adducts formed from phospholipid-esterified 9,12-dioxo-10( E)-dodecenoic acid (KODA), 9-hydroxy, 12-oxo-10( E)-dodecenoic acid (HODA), 7-oxoheptanoic acid, 8-oxooctanoic acid, and 9-oxononanoic acid were identified. Free radical oxidations of isolated HDL also generated adducts with 4-hydroxynonenal (HNE) and other noncarboxylated electrophiles, but these were only sporadically identified in the PLPBSO-adducted ApoA1, suggesting a low stoichiometry of modification in the phospholipid-adducted protein. Both phospholipid electrophiles and HNE adducted His162, which resides in an ApoA1 domain involved in the activation of Lecithin-cholesterol acyltransferase and maturation of the HDL particle. ApoA1 lipid electrophile adducts may affect protein functions and provide useful biomarkers for oxidative stress.

Project description:The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels in the general Chinese population.A total of 1030 unrelated subjects (492 males and 538 females) aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoA1 -75 bp G>A, ApoC3 3238C>G, ApoA5 -1131T>C, ApoA5 c.553G>T and ApoA5 c.457G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Pair-wise linkage disequilibria and haplotype analysis among the five SNPs were estimated.The levels of high-density lipoprotein cholesterol (HDL-C) and ApoA1 were lower in males than in femailes (P < 0.05 for each). The allelic and genotypic frequencies of the SNPs were no significant difference between males and females except ApoC3 3238C>G. There were 11 haplotypes with a frequency >1% identified in the cluster in our population. At the global level, the haplotypes comprised of all five SNPs were significantly associated with all seven lipid traits. In particular, haplotype G-G-C-C-A (6%; in the order of ApoA5 c.553G>T, ApoA5 c.457G>A, ApoA5 -1131T>C, ApoC3 3238C>G, and ApoA1 -75bp G>A) and G-A-T-C-G (4%) showed consistent association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and the ApoA1/ApoB ratio. In addition, carriers of haplotype G-G-T-C-G (26%) had increased serum concentration of HDL-C and ApoA1, whereas carriers of G-G-C-G-G (15%) had high concentrations of TC, triglyceride (TG) and ApoB. We also found that haplotypes with five SNPs explain much more serum lipid variation than any single SNP alone, especially for TG (4.4% for haplotype vs. 2.4% for -1131T>C max based on R-square) and HDL-C (5.1% for haplotype vs. 0.9% for c.553G>T based on R-square). Serum lipid parameters were also correlated with genotypes and several environment factors.Several common SNPs and their haplotypes in the ApoA1/C3/A5 gene cluster are closely associated with modifications of serum lipid parameters in the general Chinese population.

Dataset Information

Intestinal and Hepatic Uptake of Dietary Peroxidized Lipids and Their Decomposition Products, and Their Subsequent Effects on Apolipoprotein A1 and Paraoxonase1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets