1. Antiferroptotic activity of non-oxidative dopamine.
- Author
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Wang D, Peng Y, Xie Y, Zhou B, Sun X, Kang R, and Tang D
- Subjects
- Cell Survival drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Lipid Peroxidation drug effects, Oxidation-Reduction, Cell Death drug effects, Cell Death physiology, Cell Survival physiology, Dopamine pharmacology, Iron metabolism, Lipid Peroxidation physiology
- Abstract
Dopamine is a neurotransmitter that has many functions in the nervous and immune systems. Ferroptosis is a non-apoptotic form of regulated cell death that is involved in cancer and neurodegenerative diseases. However, the role of dopamine in ferroptosis remains unidentified. Here, we show that the non-oxidative form of dopamine is a strong inhibitor of ferroptotic cell death. Dopamine dose-dependently blocked ferroptosis in cancer (PANC1 and HEY) and non-cancer (MEF and HEK293) cells following treatment with erastin, a small molecule ferroptosis inducer. Notably, dopamine reduced erastin-induced ferrous iron accumulation, glutathione depletion, and malondialdehyde production. Mechanically, dopamine increased the protein stability of glutathione peroxidase 4, a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Moreover, dopamine suppressed dopamine receptor D4 protein degradation and promoted dopamine receptor D5 gene expression. Thus, our findings uncover a novel function of dopamine in cell death and provide new insight into the regulation of iron metabolism and lipid peroxidation by neurotransmitters., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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