Feedback Inhibition of the Retinaldehyde Dehydrogenase GeneALDH1 by Retinoic Acid through Retinoic Acid Receptor α and CCAAT/Enhancer-binding Protein β *

摘要: Aldehyde dehydrogenase 1 (ALDH1) plays a major role in the biosynthesis of retinoic acid (RA), hormone required for several essential life processes. Recent evidence, using aryl hydrocarbon receptor-null mouse, suggests that elevated hepatic RA down-regulates ALDH1 unique feedback pathway to control biosynthesis. To determine mechanism suppression theALDH1 gene by RA, transactivation studies were carried out Hepa-1 mouse hepatoma cells. decreased expression an ALDH1-CAT construct containing −2536 base pairs DNA upstream transcription start site. Retinoic receptor α (RARα) transactivates promoter through complex with response-like element (RARE) located at −91/−75 bp, which bound RARα/retinoid X β heterodimer. CCAAT/enhancer-binding protein (C/EBPβ) also CCAAT box 3′ and directly adjacent RARE, is down-regulated C/EBPβ-null liver. Exposure cells results decrease C/EBPβ mRNA levels; however, there was no difference levels between wild-type AHR-null These data support model RARα activate RARE C/EBP response elements, cells, high inhibit this activation decreasing cellular C/EBPβ.