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001-es BibID:	BIBFORM106058
035-os BibID:	(cikkazonosító)8300 (scopus)85137089192 (wos)000840221800001
Első szerző:	Machado, Sarah E.
Cím:	Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1 / Machado Sarah E., Spangler Daryll, Stacks Delores A., Darley-Usmar Victor, Benavides Gloria A., Xie Min, Balla József, Zarjou Abolfazl
Dátum:	2022
ISSN:	1422-0067
Megjegyzések:	Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury. Furthermore, deletion of myocardial FtH did not affect cardiac function, assessed by measurement of left ventricular ejection fraction, on days 1, 7, and 21 post injury. To identify the modulated pathways providing cardiomyocyte protection coincident with FtH deletion, we performed unbiased transcriptomic analysis. We found that following injury, FtH deletion was associated with upregulation of several genes with anti-ferroptotic properties, including heme oxygenase-1 (HO-1) and the cystine/glutamate anti-porter (Slc7a11). These results suggested that HO-1 overexpression mitigates ferroptosis via upregulation of Slc7a11. Indeed, using transgenic mice with HO-1 overexpression, we demonstrate that overexpressed HO-1 is coupled with increased Slc7a11 expression. In conclusion, we demonstrate that following injury, myocardial FtH deletion leads to a compensatory upregulation in a number of anti-ferroptotic genes, including HO-1. Such HO-1 induction leads to overexpression of Slc7a11 and protects the heart against ischemia-reperfusion-mediated ferroptosis, preserves mitochondrial function, and overall function of the myocardium.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	International Journal Of Molecular Sciences. - 23 : 15 (2022), p. 1-17. -
További szerzők:	Spangler, Daryll Stacks, Delores A. Darley-Usmar, Victor Benavides, Gloria A. Xie, Min Balla József (1959-) (belgyógyász, nephrológus) Zarjou, Abolfazl (1979-) (kutató orvos)
Pályázati támogatás:	TKP2021-EGA-20 Egyéb OTKA-132828 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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