Effects of Wine and Tyrosol on the Lipid Metabolic Profile of Subjects at Risk of Cardiovascular Disease: Potential Cardioprotective Role of Ceramides.
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ABSTRACT:
SUBMITTER: Rodriguez-Morato J
PROVIDER: S-EPMC8614856 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The effects of the short-chain ceramides D-erythro-N-acetylsphingosine (C(2)-ceramide), 6-[N-(7-nitrobenz-2-oxa-1, 3-diazole-4-yl)amino]hexanoyl-D-erythro-sphingosine(NBD-ceramide) and N-[4,4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoyl]-D-erythro-sphingosine (DMB-ceramide) on the incorporation of [(14)C]acetate into baby-hamster kidney (BHK) fibroblasts have been examined. C(2)-ceramide at concentrations up to 20 microM caused an inhibition of synthesis of phosphatidylcholine (PtdCho), sphingolipids and cholesterol within 2 h. Similar effects in BHK cells were seen using other radioactive tracers ([(3)H]water, [(3)H]palmitate and [(3)H]choline) and using HL60 cells labelled with [(14)C]acetate. The inhibition of PtdCho synthesis corresponded to an accumulation of label in diacylglycerol and triacylglycerol, probably as a consequence of cytidylyltransferase blockade. With [(3)H]choline label, the decrease in sphingomyelin synthesis could be partly accounted for by accumulation of a slow-moving lipid, likely to be C(2)-sphingomyelin. NBD-ceramide also reduced sphingomyelin and cholesterol biosynthesis, but had much less effect on PtdCho and acylglycerols. In contrast, the only apparent effect of DMB-ceramide was to inhibit synthesis of sphingomyelin, with a reciprocal increase in DMB-sphingomyelin synthesis. However, all of these short-chain ceramides caused massive apoptosis after 18 h, whereas addition of N-acetyldihydrosphingosine or elevation of natural ceramide by treatment of cells with sphingomyelinase had little effect on lipid synthesis or apoptosis. The present findings suggest that the apoptotic effect of short-chain ceramides is sometimes associated with inhibition of cytidylyltransferase, but is more closely correlated with a competitive inhibition of normal sphingomyelin biosynthesis.
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Project description:BACKGROUND: Dyslipidemia is a common metabolic disorder that may result from abnormalities in the synthesis, processing and catabolism of lipoprotein particles. Disorders of lipoprotein concentrations and elevated concentration of oxidized lipoproteins (oxLDL) are risk factors in the pathogenesis of cardiovascular diseases (CVD). CD36 plays an important role in lipid metabolism and polymorphisms in the CD36 gene are related to cardiovascular risk factors. The purpose of this study was to evaluate whether there is an association between genotypes and haplotypes of five polymorphisms in the CD36 gene with lipid levels in young normal-weight subjects. METHODS: A total of 232 unrelated subjects with normal-weight of 18 to 25 years old (157 women and 75 men) were randomly selected. The lipid profile and glucose levels were measured by enzymatic colorimetric assays. Genotyping of the polymorphisms -33137A/G (rs1984112), -31118G/A (rs1761667), -22674 T/C (rs2151916), 27645 Ins/Del (rs3840546) and 30294G/C (rs1049673) in the CD36 receptor gene was performed by polymerase chain reaction and restriction fragment length polymorphism, linkage disequilibrium analysis among the five polymorphisms and an analysis of haplotype were estimated. RESULTS: HDL-C levels was lower in men than in women (P =?0.03). However, the median oxLDL levels in men was higher than in women (P =?0.05). There was no significant difference in the levels of TC, TG, LDL-C and glucose (P >?0.05). HDL-C levels were lower in the subjects with TC genotype of polymorphism -22674 T/C (P =?0.04), but the carriers of TT genotype had lower oxLDL levels (P =?0.01). LDL-C levels were higher in young carriers of CC genotype for 30294G/C polymorphism than non-carriers (P =?0.03). The subjects carrying the AATDC haplotype had 3.2 times presumably higher risk of LDL-C >?100 mg/dL than the carrying the AGTIG haplotype (P =?0.02), whereas the subjects carrying the AATIC haplotype had 2.0 times presumably higher risk of TC >?200 mg/dL than the carrying the AGTIC haplotype (P =?0.02). CONCLUSION: The study provides evidence of a genetic association of CD36 haplotypes with the variability in LDL-C and TC levels in a sample of normal-weight subjects.
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2012-10-25 | E-GEOD-41810 | biostudies-arrayexpress