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

Kohei Yamashita; Yuichiro Hagiya; Motowo Nakajima; Masahiro Ishizuka; Tohru Tanaka; Shun-Ichiro Ogura

doi:10.1016/j.fob.2014.03.010

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

FEBS Open Bio. 2014 Mar 26:4:347-52. doi: 10.1016/j.fob.2014.03.010. eCollection 2014.

Authors

Kohei Yamashita¹, Yuichiro Hagiya¹, Motowo Nakajima², Masahiro Ishizuka², Tohru Tanaka², Shun-Ichiro Ogura¹

Affiliations

¹ Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B102, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
² SBI Pharmaceuticals CO., LTD., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo 106-6020, Japan.

Abstract

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.

Keywords: 5-Aminolevulinic acid; ALA, 5-aminolevulinic acid; Circadian rhythms; Ct, cycle threshold; DMEM, Dulbecco’s modified Eagle’s Medium; HPLC, high-performance liquid chromatography; Porphyrin metabolism; PpIX, protoporphyrin IX; REV-ERBα; SFC, sodium ferrous citrate.