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
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
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