ACMSD is a tryptophan metabolic key enzyme. HNF4α regulates the transcription of some energy-metabolic enzymes by cooperating with PGC1α, a major transcriptional co-regulator involved in energy metabolism. In this study, we investigated the involvement of PGC1α in Acmsd expression through cooperation with HNF4α. Luciferase reporter assay was performed in NIH3T3 cells using a reporter vector containing HNF4α responsive elements in the Acmsd 5' upstream transcriptional regulatory region together with HNF4α and/or PGC1α expression vectors. The Acmsd luciferase reporter activity was greatly elevated by co-overexpression of HNF4α and PGC1α in NIH3T3 cells. Moreover, the expression level of Acmsd mRNA was significantly increased by co-overexpression of HNF4α and PGC1α in primary hepatocytes compared with expression of either HNF4α or PGC1α alone. These results indicate that PGC1α is involved in Acmsd expression through cooperation with HNF4α.
Keywords: ACMSD; HNF4α; NAD; Nicotinamide; PGC1α; Quinolinate; Tryptophan.