Abstract: TH-PO632
A Uremic Toxin, 3-Carboxy-4-Methyl-5-Propyl-2-Furanpropionate, Induces Cell Ferroptosis in Human Proximal Tubular Epithelial Cells via Reduced Glutathione Peroxidase 4 and Glutathione
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Park, Jung Sun, Chonnam National University Medical School , Gwangju, Korea (the Republic of)
- Choi, Hoon In, Chonnam National University Medical School , Gwangju, Korea (the Republic of)
- Kim, Donghyun, Chonnam National University Hospital, Gwangju, Korea (the Republic of)
- Kim, Chang Seong, Chonnam National University Medical School , Gwangju, Korea (the Republic of)
- Bae, Eun Hui, Chonnam National University Hospital, Gwangju, Korea (the Republic of)
- Ma, Seong Kwon, Chonnam National University Medical School , Gwangju, Korea (the Republic of)
- Kim, Soo Wan, Chonnam National University Medical School , Gwangju, Korea (the Republic of)
Background
3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) was a uremic toxin metabolite of furan fatty acid that causes oxidative stress and accelerates the progression of renal failure. Ferroptosis is a form of cell death induced by accumulation of iron-dependent lipid-reactive oxygen species and inhibition of glutathione peroxidase 4 (GPX4). We investigated whether uremic toxin, CMPF affects renal proximal tubular cell damage by ferroptosis, a non-apoptotic form.
Methods
The fluorescent dye 2¢, 7¢-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following CMPF administration in human renal proximal tubular epithelial (HK-2) cells. The effects of CMPF on cell viability was determined using EZ-CyTox assays, and level of glutathione were determined by luminescence using the GSH/GSSH assay. glutathione peroxidase 4 (GPX4) proteins was determined by semiquantitative immunoblotting.
Results
Treatment of CMPF in HK-2 cells promoted the production of ROS. In addition, treatment with CMPF not only reduced the level of GSH but also decreased the expression of GPX4 protein. The ferroptosis inhibitor, lipophilic antioxidant, Fer-1, inhibited CMPF-induced ferroptosis, and iron chelators, DFO, also attenuated CMPF-induced ferroptosis in HK-2 cells.
Conclusion
The results of this study show that CMPF in HK-2 cells promoted the production of reactive oxygen species (ROS) and reduced the levels of GSH and GPX4 expression, resulting in cell death due to ferroptosis.
Funding
- Government Support - Non-U.S.