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

The nuclear receptor, REV-ERB alpha, 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-ERB alpha and its target genes. When exposed to ALA, the human lung diploid cell line, WI-38, exhibited activation of REV-ERB alpha and repression of the transcription of REV-ERB alpha target genes, including BMAL1, an essential component of the circadian oscillator. Moreover, co-incubation of sodium ferrous citrate (SFC) and ALA also activated REV-ERB alpha and repressed the transcription of REV-ERB alpha target genes. These results indicate that ALA regulates human circadian rhythms via REV-ERB alpha. (C) 2014 The Authors. Published by Elsevier B.V.