Nuclear magnetic resonance affects the circadian clock and hypoxia-inducible factor isoforms in zebrafish

Abstract

Nuclear magnetic resonance (NMR) is used for magnetic resonance imaging and, at a lower intensity, as therapy for the treatment of musculoskeletal disorders. Due to the involvement of the circadian clock protein CRYPTOCHROME in the magnetic orientation of animals, it was repeatedly assumed that magnetic fields might affect the circadian rhythm of cells and organisms. Since circadian time keeping and hypoxic signaling are mutually intertwined, we investigated the effects of NMR on both cellular pathways in zebrafish fibroblast cells and larvae. In cells, basal mRNA expression of <i>cryptochrome1aa</i> was increased and oscillations of <i>cryptochrome1aa</i> and <i>period1b</i> were shifted in phase, while those of <i>clock1a</i> and <i>period2</i> remained unaffected. Similarly, circadian oscillations of <i>cryptochrome1aa</i> and <i>period1b</i> were restored in zebrafish larvae, while those of <i>clock1a</i> and <i>period2</i> remained unaltered. NMR also restored the circadian expression of the hypoxia-inducible factor (Hif) isoforms Hif-1α and Hif-3α at the mRNA and protein level, but had no effect on the expression of Hif-2α. Thus, NMR-mediated effects might differ substantially from the light-induced reset of the circadian clock in the same species and therefore represent an additional operation mode of the cellular clock, enabling distinct processing of photic and magnetic information.