Antiferroptotic activity of non-oxidative dopamine

Ding Wang, Yingpeng Peng, Yangchun Xie, Borong Zhou, Xiaofang Sun, Rui Kang, Daolin Tang

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)602-607
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume480
Issue number4
DOIs
StatePublished - Nov 25 2016
Externally publishedYes

    Fingerprint

Keywords

  • Dopamine
  • Ferroptosis
  • Iron
  • Lipid peroxidation
  • Receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this