Hemin and iron increase synthesis and trigger export of xanthine oxidoreductase from hepatocytes to the circulation
Autor: | Evan R. DeVallance, Heidi M. Schmidt, Madison Seman, Sara E. Lewis, Katherine C. Wood, Schuyler D. Vickers, Scott A. Hahn, Murugesan Velayutham, Emily A. Hileman, Dario A. Vitturi, Roberta Leonardi, Adam C. Straub, Eric E. Kelley |
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Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Redox Biology, Vol 67, Iss , Pp 102866- (2023) |
Druh dokumentu: | article |
ISSN: | 2213-2317 54264804 |
DOI: | 10.1016/j.redox.2023.102866 |
Popis: | We recently reported a previously unknown salutary role for xanthine oxidoreductase (XOR) in intravascular heme overload whereby hepatocellular export of XOR to the circulation was identified as a seminal step in affording protection. However, the cellular signaling and export mechanisms underpinning this process were not identified. Here, we present novel data showing hepatocytes upregulate XOR expression/protein abundance and actively release it to the extracellular compartment following exposure to hemopexin-bound hemin, hemin or free iron. For example, murine (AML-12 cells) hepatocytes treated with hemin (10 μM) exported XOR to the medium in the absence of cell death or loss of membrane integrity (2.0 ± 1.0 vs 16 ± 9 μU/mL p controls for both, p |
Databáze: | Directory of Open Access Journals |
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