Antiferroptotic activity of non-oxidative dopamine
| Autor: | Yingpeng Peng, Borong Zhou, Rui Kang, Yangchun Xie, Ding Wang, Xiaofang Sun, Daolin Tang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Survival Dopamine Iron Biophysics Protein degradation Biology GPX4 Biochemistry Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound Dopamine receptor D5 medicine Dopamine receptor D4 Humans Neurotransmitter Molecular Biology Cells Cultured Cell Death Dose-Response Relationship Drug Dopaminergic Cell Biology Cell biology 030104 developmental biology chemistry biology.protein Lipid Peroxidation Oxidation-Reduction medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 480:602-607 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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