ALKBH5 insufficiency protects against ferroptosis-driven cisplatin-induced renal cytotoxicity DOI Creative Commons
Yu Zhu, Yanyan Jin, Xue He

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 18, 2024

In the clinical setting, cisplatin-induced nephrotoxicity primarily manifests as acute kidney injury (AKI). Recent studies have indicated that ferroptosis, a type of iron-dependent cell death, is closely involved in cisplatin nephrotoxicity. AlkB homologue 5 (ALKBH5), an N6-methyladenosine (m6A) eraser protein expressed various tissues, including kidneys, has been implicated this process. However, specific role ALKBH5 remains unknown. Our findings was upregulated AKI, and vivo study results were consistent with vitro study. Additionally, knockout transgenic animals found to mitigate renal dysfunction, whereas its knock-in exacerbated effects. revealed controls traditional ferroptosis metabolic pathway, leading worsening AKI experiments conducted both vitro. The efficacy pharmacological intervention targeting animal models demonstrated, ALKBH5-based gene therapy confirmed these displayed renoprotective effects against AKI. conclusion, highlighted crucial key regulator Overall, our research demonstrates significant impact controlling suggesting focusing on could be promising approach for treating cisplatin-related damage.

Language: Английский

Lipid Peroxidation, Ferroptosis and Antioxidants DOI
Noriko Noguchi, Yoshiro Saito,

Etsuo Niki

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
ALKBH5 insufficiency protects against ferroptosis-driven cisplatin-induced renal cytotoxicity DOI Creative Commons
Yu Zhu, Yanyan Jin, Xue He

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 18, 2024

In the clinical setting, cisplatin-induced nephrotoxicity primarily manifests as acute kidney injury (AKI). Recent studies have indicated that ferroptosis, a type of iron-dependent cell death, is closely involved in cisplatin nephrotoxicity. AlkB homologue 5 (ALKBH5), an N6-methyladenosine (m6A) eraser protein expressed various tissues, including kidneys, has been implicated this process. However, specific role ALKBH5 remains unknown. Our findings was upregulated AKI, and vivo study results were consistent with vitro study. Additionally, knockout transgenic animals found to mitigate renal dysfunction, whereas its knock-in exacerbated effects. revealed controls traditional ferroptosis metabolic pathway, leading worsening AKI experiments conducted both vitro. The efficacy pharmacological intervention targeting animal models demonstrated, ALKBH5-based gene therapy confirmed these displayed renoprotective effects against AKI. conclusion, highlighted crucial key regulator Overall, our research demonstrates significant impact controlling suggesting focusing on could be promising approach for treating cisplatin-related damage.

Language: Английский

Citations

0