The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells
Open accessAbstract
Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is protective against AKI because of its antiapoptotic and anti-inflammatory properties. However, the role of HO-1 in regulating ferroptosis is unclear. The purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic cell death in renal proximal tubule cells (PTCs). Immortalized PTCs obtained from HO-1+/+ and HO-1−/− mice were treated with erastin or RSL3, ferroptosis inducers, in the presence or absence of antioxidants, an iron source, or an iron chelator. Cells were assessed for changes in morphology and metabolic activity as an indicator of cell viability. Treatment of HO-1+/+ PTCs with erastin resulted in a time- and dose-dependent increase in HO-1 gene expression and protein levels compared with vehicle-treated controls. HO-1−/− cells showed increased dose-dependent erastin- or RSL3-induced cell death in comparison to HO-1+/+ PTCs. Iron supplementation with ferric ammonium citrate in erastin-treated cells decreased cell viability further in HO-1−/− PTCs compared with HO-1+/+ cells. Cotreatment with ferrostatin-1 (ferroptosis inhibitor), deferoxamine (iron chelator), or N-acetyl-l-cysteine (glutathione replenisher) significantly increased cell viability and attenuated erastin-induced ferroptosis in both HO-1+/+ and HO-1−/− PTCs. These results demonstrate an important antiferroptotic role of HO-1 in renal epithelial cells.
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Role of GPX4 in ferroptosis and its pharmacological implication
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Metadata
- Authors
- Adedoyin, O., Boddu, R., Traylor, A., Lever, J. M., Bolisetty, S., George, J. F., & Agarwal, A.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2018-05-01
- Volume
- 314
- Issue
- 5
- Pages
- F702-F714
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2616772553
- Cited by
- 368
- References
- 18
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- green
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- Adedoyin, O., Boddu, R., Traylor, A., Lever, J. M., Bolisetty, S., George, J. F., & Agarwal, A. (2018). Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. American Journal of Physiology-Renal Physiology. https://doi.org/10.1152/ajprenal.00044.2017
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