Ginsenoside Rg1 Suppresses Ferroptosis of Renal Tubular Epithelial Cells in Sepsis-induced Acute Kidney Injury via the FSP1-CoQ10- NAD(P)H Pathway
- Авторы: Guo J.1, Chen L.2, Ma M.2
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Учреждения:
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University
- Department of Critical Care Medicine, Union Jiangbei Hospital,, Huazhong University of Science and Technology
- Выпуск: Том 31, № 15 (2024)
- Страницы: 2119-2132
- Раздел: Anti-Infectives and Infectious Diseases
- URL: https://permmedjournal.ru/0929-8673/article/view/644426
- DOI: https://doi.org/10.2174/0929867330666230607125054
- ID: 644426
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Аннотация
Introduction:Sepsis-induced acute kidney injury is related to an increased mortality rate by modulating ferroptosis through ginsenoside Rg1. In this study, we explored the specific mechanism of it.
Methods:Human renal tubular epithelial cells (HK-2) were transfected with oe-ferroptosis suppressor protein 1 and treated with lipopolysaccharide for ferroptosis induction, and they were then treated with ginsenoside Rg1 and ferroptosis suppressor protein 1 inhibitor. Ferroptosis suppressor protein 1, CoQ10, CoQ10H2, and intracellular NADH levels in HK-2 cells were assessed by Western blot, ELISA kit, and NAD/NADH kit. NAD+/NADH ratio was also calculated, and 4-Hydroxynonal fluorescence intensity was assessed by immunofluorescence. HK-2 cell viability and death were assessed by CCK-8 and propidium iodide staining. Ferroptosis, lipid peroxidation, and reactive oxygen species accumulation were assessed by Western blot, kits, flow cytometry, and C11 BODIPY 581/591 molecular probe. Sepsis rat models were established by cecal ligation and perforation to investigate whether ginsenoside Rg1 regulated the ferroptosis suppressor protein 1-CoQ10-NAD(P)H pathway in vivo.
Results:LPS treatment diminished ferroptosis suppressor protein 1, CoQ10, CoQ10H2, and NADH contents in HK-2 cells, while facilitating NAD+/NADH ratio and relative 4- Hydroxynonal fluorescence intensity. FSP1 overexpression inhibited lipopolysaccharideinduced lipid peroxidation in HK-2 cells via the ferroptosis suppressor protein 1-CoQ10- NAD(P)H pathway. The ferroptosis suppressor protein 1-CoQ10-NAD(P)H pathway suppressed lipopolysaccharide-induced ferroptosis in HK-2 cells. Ginsenoside Rg1 alleviated ferroptosis in HK-2 cells by regulating the ferroptosis suppressor protein 1-CoQ10- NAD(P)H pathway. Moreover, ginsenoside Rg1 regulated the ferroptosis suppressor protein 1-CoQ10-NAD(P)H pathway in vivo.
Conclusion:Ginsenoside Rg1 alleviated sepsis-induced acute kidney injury by blocking renal tubular epithelial cell ferroptosis via the ferroptosis suppressor protein 1-CoQ10- NAD(P)H pathway.
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Об авторах
Jun Guo
Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University
Автор, ответственный за переписку.
Email: info@benthamscience.net
Long Chen
Department of Critical Care Medicine, Union Jiangbei Hospital,, Huazhong University of Science and Technology
Email: info@benthamscience.net
Min Ma
Department of Critical Care Medicine, Union Jiangbei Hospital,, Huazhong University of Science and Technology
Email: info@benthamscience.net
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