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Erschienen in:
01.03.2008 | ORIGINAL CONTRIBUTION
Down-regulation of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase by polyunsaturated fatty acids in hepatocytes is not mediated by PPARα
Erschienen in: European Journal of Nutrition | Ausgabe 2/2008
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Background
α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is a key enzyme in NAD biosynthesis from tryptophan. Dietary polyunsaturated fatty acids (PUFA) have been shown to suppress hepatic ACMSD activity and its mRNA level in rat. However the mechanism of the suppressive action has not been clarified yet. Although the phenomena that fatty acids suppress the expression of ACMSD in rat liver have been established in vivo experiment, it is still obscure whether the effect of fatty acids on the expression of the enzyme is caused by its direct or indirect action, because there have been very few investigations performed in vitro.
Aim of the study
In this study, to examine whether down-regulation of ACMSD mRNA by PUFA involves peroxisome proliferator-activated receptor (PPAR) α mediated mechanism or not, we investigated the effect of PUFA on the ACMSD expression by using primary cultured rat hepatocytes.
Methods
For this purpose we investigated the effect of PUFA (linoleic acid and eicosapentanoic acid) on the ACMSD mRNA level in primary-cultured rat hepatocytes and compared its effect with that of WY-14,643 (a PPARα agonist). After the incubation of hepatocytes with fatty acids, WY-14,643 and/or MK886 (a PPARα antagonist), mRNA levels of ACMSD and a peroxisome marker enzyme acyl-CoA oxidase (ACO) were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) method.
Results
ACMSD mRNA level in primary hepatocytes were decreased by the incubation with high concentrations of linoleic acid, eicosapentaenoic acid (EPA) and WY-14,643. The appearance of ACO mRNA by WY-14,643 was remarkably increased, and those by linoleic acid and EPA were increased less than that by WY-14,643. Moreover, the suppression of ACMSD mRNA and the augmentation of ACO mRNA by WY-14,643 were inhibited by MK886, but the suppression by PUFA was not substantially affected by MK886.
Conclusions
The present study suggesting that the mechanism of decrease in ACMSD mRNA level by PUFA was different from that by WY-14,643, and that there would be any pathway other than PPARα mediated one for PUFA to regulate ACMSD expression.