Title:Ginsenoside Rg1 Suppresses Ferroptosis of Renal Tubular Epithelial
Cells in Sepsis-induced Acute Kidney Injury via the FSP1-CoQ10-
NAD(P)H Pathway
Volume: 31
Issue: 15
关键词:
脓毒症,急性肾损伤,人参皂苷Rg1,铁下垂FSP1-CoQ10-NAD(P)H途径,HK-2细胞,脂多糖,4-HNE。
摘要:
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.