Platycodin D regulates high glucose-induced ferroptosis of HK-2 cells through glutathione peroxidase 4 (GPX4).
Bioengineered
; 13(3): 6627-6637, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35226829
Diabetic nephropathy (DN) is associated with inflammation. Platycodin D (PD) demonstrates anti-inflammatory activity. However, whether PD affects DN remains to be explored. Here, we aimed to discuss the role of PD in DN and its underlying mechanisms. High glucose (HG)-induced HK-2 cells were treated with PD, and cell viability was assessed using the Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Ferroptosis-related factors such as lactate dehydrogenase (LDH) activity, lipid reactive oxygen species (ROS), iron (Fe2+) level, GSH level, and malondialdehyde (MDA) level were evaluated. Cell death was evaluated using the TUNEL assay. GPX4 expression was evaluated using Quantitative Real-time PCR (qRT-PCR) and Western blotting analysis. The results indicated that HG increased LDH activity, lipid ROS production, Fe2+ levels, and MDA levels and decreased GSH levels, suggesting that the HG condition induced ferroptosis. PD treatment inhibited ferroptosis in HG-induced cells, downregulated ACSL4 and TFR1 expression, and upregulated FTH-1 and SLC7A11 expression. PD reversed the effects of HG condition on cell death. Moreover, GPX4 expression was downregulated in HG-stimulated cells. Furthermore, we substantiated that PD suppressed ferroptosis by modulating GPX4 expression. In conclusion, PD inhibited ferroptosis in HG-induced HK-2 cells by upregulating GPX4 expression, suggesting that PD may be an effective drug for the clinical treatment of DN.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
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Triterpenos
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Ferroptose
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Fosfolipídeo Hidroperóxido Glutationa Peroxidase
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Glucose
Limite:
Humans
Idioma:
En
Revista:
Bioengineered
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos