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001-es BibID:	BIBFORM051960
Első szerző:	Bolisetty, Subhashini
Cím:	Mitochondria-targeted heme oxygenase-1 decreases oxidative stress in renal epithelial cells / Subhashini Bolisetty, Amie Traylor, Abolfazl Zarjou, Michelle S. Johnson, Gloria A. Benavides, Karina Ricart, Ravindra Boddu, Ray D. Moore, Aimee Landar, Stephen Barnes, Victor Darley-Usmar, Anupam Agarwal
Dátum:	2013
ISSN:	1931-857X 1522-1466
Megjegyzések:	Mitochondria are both a source and target of the actions of reactive oxygen species and possess a complex system of inter-related antioxidants that control redox signaling and protect against oxidative stress. Interestingly, the antioxidant enzyme heme oxygenase-1 (HO-1) is not present in the mitochondria despite the fact that the organelle is the site of heme synthesis and contains multiple heme proteins. Detoxification of heme is an important protective mechanism since the reaction of heme with hydrogen peroxide generates pro-oxidant ferryl species capable of propagating oxidative stress and ultimately cell death. We therefore hypothesized that a mitochondrially localized HO-1 would be cytoprotective. To test this, we generated a mitochondria-targeted HO-1 cell line by transfecting HEK293 cells with a plasmid construct containing the manganese superoxide dismutase mitochondria leader sequence fused to HO-1 cDNA (Mito-HO-1). Nontargeted HO-1-overexpressing cells were generated by transfecting HO-1 cDNA (HO-1) or empty vector (Vector). Mitochondrial localization of HO-1 with increased HO activity in the mitochondrial fraction of Mito-HO-1 cells was observed, but a significant decrease in the expression of heme-containing proteins occurred in these cells. Both cytosolic HO-1- and Mito-HO-1-expressing cells were protected against hypoxia-dependent cell death and loss of mitochondrial membrane potential, but these effects were more pronounced with Mito-HO-1. Furthermore, decrement in production of tricarboxylic acid cycle intermediates following hypoxia was significantly mitigated in Mito-HO-1 cells. These data suggest that specific mitochondrially targeted HO-1 under acute pathological conditions may have beneficial effects, but the selective advantage of long-term expression is constrained by a negative impact on the synthesis of heme-containing mitochondrial proteins.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	American Journal of Physiology. Renal Physiology. - 305 : 3 (2013), p. F255-F264. -
További szerzők:	Traylor, Amie Zarjou, Abolfazl (1979-) (kutató orvos) Johnson, Michelle S. Benavides, Gloria A. Ricart, Karina Boddu, Ravindra Moore, Ray D. Landar, Aimee Barnes, Stephen Darley-Usmar, Victor Agarwal, Anupam
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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
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