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Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid.
J Neurosci Res. 2003 Oct 01; 74(1):134-41.JN

Abstract

The mRNA expression levels of acyl-CoA oxidase (AOX), a key enzyme in very-long-chain fatty acid peroxisomal oxidation, and of peroxisome proliferator-activated receptor-delta (PPAR-delta), a nuclear receptor possibly involved in the gene regulation of brain lipid metabolism, were determined in human Y79 retinoblastoma cells by using real-time quantitative polymerase chain reaction. Cells were dosed with alpha-linolenic acid (18:3n-3), the essential metabolic precursor of the n-3 polyunsaturated fatty acid series that normally gives rise through terminal peroxisomal oxidation to the synthesis of membrane docosahexaenoic acid (22:6n-3, or DHA). The AOX and PPAR-delta relative expression levels increased 2.3 and 3.4 times, respectively, upon dosing of cells with 7 microM 18:3n-3, whereas AOX cDNA abundance decreased by 50% upon dosing with 70 microM 18:3n-3. Concurrently, the DHA content increased by 23% in the membrane ethanolamine-phosphoglycerides from cells dosed with 7 microM 18:3n-3, whereas it decreased by 38% upon dosing with 70 microM 18:3n-3. The DHA's upstream precursors (20:5n-3 and 22:5n-3) both accumulated in cells dosed with 7 or 70 microM 18:3n-3. The 18:3n-3-induced changes in membrane phospholipid fatty acid composition support the hypothesis that the terminal peroxisomal step of n-3 conversion is rate limiting in the Y79 line. The concurrent 7 microM 18:3n-3-induced increase of mRNAs encoding for AOX and for PPAR-delta suggests that 18:3n-3 (or its metabolites) at low concentration could trigger its proper conversion to DHA, possibly through activation of PPAR-delta-mediated transcription of AOX. Decreased membrane DHA content and mRNA expression level of AOX in 70-microM 18:3n-3-dosed cells corroborated the relationship between AOX expression and DHA synthesis and suggested that simultaneous down-regulating events occurred at high concentrations of 18:3n-3.

Authors+Show Affiliations

Nutrition and Food Safety, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

13130515

Citation

Langelier, Bénédicte, et al. "Docosahexaenoic Acid Membrane Content and mRNA Expression of acyl-CoA Oxidase and of Peroxisome Proliferator-activated Receptor-delta Are Modulated in Y79 Retinoblastoma Cells Differently By Low and High Doses of Alpha-linolenic Acid." Journal of Neuroscience Research, vol. 74, no. 1, 2003, pp. 134-41.
Langelier B, Furet JP, Perruchot MH, et al. Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid. J Neurosci Res. 2003;74(1):134-41.
Langelier, B., Furet, J. P., Perruchot, M. H., & Alessandri, J. M. (2003). Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid. Journal of Neuroscience Research, 74(1), 134-41.
Langelier B, et al. Docosahexaenoic Acid Membrane Content and mRNA Expression of acyl-CoA Oxidase and of Peroxisome Proliferator-activated Receptor-delta Are Modulated in Y79 Retinoblastoma Cells Differently By Low and High Doses of Alpha-linolenic Acid. J Neurosci Res. 2003 Oct 1;74(1):134-41. PubMed PMID: 13130515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid. AU - Langelier,Bénédicte, AU - Furet,Jean-Pierre, AU - Perruchot,Marie-Hélène, AU - Alessandri,Jean-Marc, PY - 2003/9/18/pubmed PY - 2003/11/11/medline PY - 2003/9/18/entrez SP - 134 EP - 41 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 74 IS - 1 N2 - The mRNA expression levels of acyl-CoA oxidase (AOX), a key enzyme in very-long-chain fatty acid peroxisomal oxidation, and of peroxisome proliferator-activated receptor-delta (PPAR-delta), a nuclear receptor possibly involved in the gene regulation of brain lipid metabolism, were determined in human Y79 retinoblastoma cells by using real-time quantitative polymerase chain reaction. Cells were dosed with alpha-linolenic acid (18:3n-3), the essential metabolic precursor of the n-3 polyunsaturated fatty acid series that normally gives rise through terminal peroxisomal oxidation to the synthesis of membrane docosahexaenoic acid (22:6n-3, or DHA). The AOX and PPAR-delta relative expression levels increased 2.3 and 3.4 times, respectively, upon dosing of cells with 7 microM 18:3n-3, whereas AOX cDNA abundance decreased by 50% upon dosing with 70 microM 18:3n-3. Concurrently, the DHA content increased by 23% in the membrane ethanolamine-phosphoglycerides from cells dosed with 7 microM 18:3n-3, whereas it decreased by 38% upon dosing with 70 microM 18:3n-3. The DHA's upstream precursors (20:5n-3 and 22:5n-3) both accumulated in cells dosed with 7 or 70 microM 18:3n-3. The 18:3n-3-induced changes in membrane phospholipid fatty acid composition support the hypothesis that the terminal peroxisomal step of n-3 conversion is rate limiting in the Y79 line. The concurrent 7 microM 18:3n-3-induced increase of mRNAs encoding for AOX and for PPAR-delta suggests that 18:3n-3 (or its metabolites) at low concentration could trigger its proper conversion to DHA, possibly through activation of PPAR-delta-mediated transcription of AOX. Decreased membrane DHA content and mRNA expression level of AOX in 70-microM 18:3n-3-dosed cells corroborated the relationship between AOX expression and DHA synthesis and suggested that simultaneous down-regulating events occurred at high concentrations of 18:3n-3. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/13130515/Docosahexaenoic_acid_membrane_content_and_mRNA_expression_of_acyl_CoA_oxidase_and_of_peroxisome_proliferator_activated_receptor_delta_are_modulated_in_Y79_retinoblastoma_cells_differently_by_low_and_high_doses_of_alpha_linolenic_acid_ L2 - https://doi.org/10.1002/jnr.10714 DB - PRIME DP - Unbound Medicine ER -