Germacrone protects renal tubular cells against ferroptotic death and ROS release by re-activating mitophagy in diabetic nephropathy.
Free Radic Res
; 57(6-12): 413-429, 2023.
Article
em En
| MEDLINE
| ID: mdl-37897414
ABSTRACT
Mitophagy is a critical intracellular event during the progression of diabetic nephropathy (DN). Our previous study demonstrated that germacrone has anti-ferroptotic properties and is a potential therapeutic agent for DN. However, the relationship among germacrone, mitophagy, and ferroptosis in DN remains unclear. In this study, the data confirmed that germacrone ameliorates high glucose (HG)-induced ferroptosis through limiting Fe (2+) content and lipid reactive oxygen species (ROS) accumulation in human kidney 2 (HK-2) cells. Germacrone reversed HG-mediated inhibition of mitophagy. Mitophagy inhibition and anabatic mitochondrial ROS abrogate germacrone-mediated protective effects against ferroptotic death, resulting in the subsequent activation of mitochondrial DNA (mtDNA) cytosolic leakage-induced stimulator of interferon response CGAMP interactor 1 (STING) signaling. The combination of a mitochondrial ROS antagonist and germacrone acts synergistically to alleviate the ferroptotic death of tubular cells and DN symptoms. In summary, germacrone ameliorated ferroptotic death in tubular cells by reactivating mitophagy and inhibiting mtDNA-STING signaling in DN. This study provides a novel insight into germacrone-mediated protection against DN progression and further confirms that antioxidant pharmacological strategies facilitate the treatment of DN.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus
/
Nefropatias Diabéticas
Limite:
Humans
Idioma:
En
Revista:
Free Radic Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2023
Tipo de documento:
Article