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Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8300
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- 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.
- Subjects :
- Myocardium
Organic Chemistry
Membrane Proteins
Stroke Volume
General Medicine
heme oxygenase-1
ferroptosis
ferritin
Slc7a11
Ventricular Function, Left
Catalysis
Computer Science Applications
Inorganic Chemistry
Mice
Apoferritins
Heme Oxygenase (Decyclizing)
Animals
Myocytes, Cardiac
Physical and Theoretical Chemistry
Molecular Biology
Heme Oxygenase-1
Spectroscopy
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....7b8a9d8264f649c55f2f3f9a3e9df7eb
- Full Text :
- https://doi.org/10.3390/ijms23158300