ABSTRACT
Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB.
Subject(s)
DNA Damage , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Fatty Acids, Omega-3/blood , Adolescent , Brazil , Child , Class I Phosphatidylinositol 3-Kinases/blood , Class Ia Phosphatidylinositol 3-Kinase/blood , Cross-Sectional Studies , Cyclin C/blood , Cyclin-Dependent Kinase 8/blood , Female , Humans , Hydrolases/blood , Inflammation/metabolism , Male , Protein Kinase C beta/blood , ProteomicsABSTRACT
This study aimed to investigate the association between DNA damage and blood levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), retinol, beta-carotene and riboflavin in Brazilian children and adolescents. Subjects (n = 140) were healthy boys and girls aged 9 to 13 years in Ribeirão Preto (SP, Brazil). Data collection included anthropometry, assessment of energy intake and blood sampling. DNA damage was evaluated by single-cell gel electrophoresis (comet assay). Principal component analysis (PCA) was used to verify associations between blood concentrations of vitamins, polyunsaturated fatty acids and DNA damage. Multiple regression analyses, k-means cluster, and analysis of covariance (ANCOVA), adjusted for confounding variables such as age, sex, energy intake, body mass index and total cholesterol (when needed), were applied to confirm the associations. PCA explained 69.4% of the inverse relationships between DNA damage and blood levels of DHA, EPA, retinol, and beta-carotene. Results were confirmed by ANCOVA and multiple regression analyses for DHA and EPA. In conclusion, omega-3-fatty acids were inversely associated with DNA damage in Brazilian children and adolescents and may be a protective factor against the development of future diseases.
Subject(s)
DNA Damage , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Adolescent , Body Mass Index , Brazil , Child , Cross-Sectional Studies , Energy Intake , Fatty Acids, Unsaturated/blood , Female , Humans , Male , Riboflavin/blood , Vitamin A/blood , Vitamins/blood , beta Carotene/bloodABSTRACT
Micronutrients and their metabolites are cofactors in proteins involved in lipid metabolism. The present study was a subproject of the Harmonized Micronutrient Project (ClinTrials.gov # NCT01823744). Twenty participants were randomly selected from 136 children and adolescents that consumed a daily dose of 12 vitamins and 5 minerals supplementation for 6 weeks. The 20 individuals were divided into two pools of 10 individuals, according to their lipid profile at baseline (Pool 1 with lower triglycerides, LDL, and VLDL). The individuals were analyzed at baseline, after 6 weeks of daily supplementation, and after 6 weeks of a washout period in relation to anthropometric, body composition, food intake, lipid profile, micronutrient levels, and iTRAQ proteomic data. Genetic ancestry and its association with vitamin serum levels were also determined. After supplementation, LDL levels decreased while alpha-tocopherol and pantothenic acid levels increased in pool 2; lipid profiles in pool 1 did not change but had higher plasma levels of pantothenic acid, pyridoxal, and pyridoxic acid. In pool 2, expression of some proteins increased, and expression of other ones decreased after intervention, while in pool 1, the same proteins responded inversely or did not change their levels. Plasma alpha-tocopherol and Native American genetic ancestry explained a significant fraction of LDL plasma levels at baseline and in response to the intervention. After intervention, changes in expression of alpha-1 antitrypsin, haptoglobin, Ig alpha-1 chain C region, plasma protease C1 inhibitor, alpha-1-acid glycoprotein 1, fibrinogen alpha, beta, and gamma-chain in individuals in pool 2 may be associated with levels of LDL and vitamin E. Vitamin E and Native American genetic ancestry may also be implicated in changes of vitamin E and LDL levels. The results of this pilot study must be validated in future studies with larger sample size or in in vitro studies.
