Mechanisms and physiological function of daily haemoglobin oxidation rhythms in red blood cells.

Autor: Beale AD; MRC Laboratory of Molecular Biology, Cambridge, UK., Hayter EA; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Crosby P; MRC Laboratory of Molecular Biology, Cambridge, UK., Valekunja UK; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Edgar RS; Department of Infectious Diseases, Imperial College London, London, UK., Chesham JE; MRC Laboratory of Molecular Biology, Cambridge, UK., Maywood ES; MRC Laboratory of Molecular Biology, Cambridge, UK., Labeed FH; Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, UK., Reddy AB; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wright KP Jr; Department of Integrative Physiology, Sleep and Chronobiology Laboratory, University of Colorado Boulder, Boulder, CO, USA., Lilley KS; Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK., Bechtold DA; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Hastings MH; MRC Laboratory of Molecular Biology, Cambridge, UK., O'Neill JS; MRC Laboratory of Molecular Biology, Cambridge, UK.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Oct 04; Vol. 42 (19), pp. e114164. Date of Electronic Publication: 2023 Aug 09.
DOI: 10.15252/embj.2023114164
Abstrakt: Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. Here, we present a novel biochemical assay for haemoglobin (Hb) oxidation status which relies on a redox-sensitive covalent haem-Hb linkage that forms during SDS-mediated cell lysis. Formation of this linkage is lowest when ferrous Hb is oxidised, in the form of ferric metHb. Daily haemoglobin oxidation rhythms are observed in mouse and human RBCs cultured in vitro, or taken from humans in vivo, and are unaffected by mutations that affect circadian rhythms in nucleated cells. These rhythms correlate with daily rhythms in core body temperature, with temperature lowest when metHb levels are highest. Raising metHb levels with dietary sodium nitrite can further decrease daytime core body temperature in mice via nitric oxide (NO) signalling. These results extend our molecular understanding of RBC circadian rhythms and suggest they contribute to the regulation of body temperature.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE