The effects of the heme precursor 5-aminolevulinic acid (ALA) on REV-ERBα activation

• REV-ERBα has a key role in circadian rhythms and requires heme as its ligand.
• Heme precursor ALA exhibited increased nuclear heme level and activation of REV-ERBα.
• ALA inhibited REV-ERBα target genes including an essential component of the circadian oscillator.

The nuclear receptor, REV-ERBα, has a key role in circadian rhythms and requires heme as its ligand. The present study determined whether the heme precursor, 5-aminolevulinic acid (ALA), affects REV-ERBα and its target genes. When exposed to ALA, the human lung diploid cell line, WI-38, exhibited activation of REV-ERBα and repression of the transcription of REV-ERBα target genes, including BMAL1, an essential component of the circadian oscillator. Moreover, co-incubation of sodium ferrous citrate (SFC) and ALA also activated REV-ERBα and repressed the transcription of REV-ERBα target genes. These results indicate that ALA regulates human circadian rhythms via REV-ERBα.