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Title: | Extensive profiling of histidine-containing dipeptides reveals species- and tissue-specific distribution and metabolism in mice, rats, and humans | Authors: | Van der Stede, Thibaux SPAAS, Jan de Jager, Sarah DE BRANDT, Jana Hansen, Camilla Stautemas, Jan Vercammen, Bjarne De Baere, Siegrid Croubels, Siska Van Assche, Charles-Henri Pastor, Berta Cillero Vandenbosch, Michiel Van Thienen, Ruud VERBOVEN, Kenneth HANSEN, Dominique Bove, Thierry Lapauw, Bruno Van Praet, Charles Decaestecker, Karel Vanaudenaerde, Bart OP 'T EIJNDE, Bert Gliemann, Lasse Hellsten, Ylva Derave, Wim |
Issue Date: | 2023 | Publisher: | WILEY | Source: | Acta Physiologica, 239 (1) (Art N° e14020) | Abstract: | AimHistidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear. MethodsUsing a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively). ResultsOur data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion. ConclusionCollectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease. | Notes: | Derave, W (corresponding author), Univ Ghent, Dept Movement & Sports Sci, Watersportlaan 2, B-9000 Ghent, Belgium. wim.derave@ugent.be |
Keywords: | carnosine;central nervous system;exercise;histidine-containing dipeptides;muscle | Document URI: | http://hdl.handle.net/1942/40757 | ISSN: | 1748-1708 | e-ISSN: | 1748-1716 | DOI: | 10.1111/apha.14020 | ISI #: | 001033778700001 | Rights: | 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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Acta Physiologica - 2023 - Van der Stede.pdf Restricted Access | Published version | 20.98 MB | Adobe PDF | View/Open Request a copy |
auteursversie.pdf Until 2024-09-30 | Peer-reviewed author version | 854.48 kB | Adobe PDF | View/Open Request a copy |
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