3 years ago

Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages

Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages
Iron is essential for many biological functions including neurotransmitter synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts tyrosine to dopamine and further to norepinephrine. As the shared chemical structure, called catechol, may potentially bind iron we questioned whether tyrosine derived hormones would impact on cellular iron homeostasis in macrophages, which are central for the maintenance of body iron homeostasis. Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect of catecholamines and found that only dopamine but neither tyrosine, nor norepinephrine, affected cellular iron homeostasis. Exposure of macrophages to dopamine increased the uptake of non-transferrin bound iron into cells. The expansion of intracellular iron upon dopamine treatment resulted in oxidative stress responses as evidenced by increased expression of nuclear factor erythroid 2-related factor (Nrf2) and hypoxia inducible factor-1α. As a consequence, the transcriptional expression of stress response genes such as heme oxygenase-1 and the iron export protein ferroportin1 were significantly increased. Genetic deletion of Nrf2 abolished these effects of dopamine. Dopamine directly affects cellular iron homeostasis by increasing iron incorporation into macrophages and subsequently promoting intracellular oxidative stress responses. Our observations are of interest for disorders involving dopamine and iron dyshomeostasis such as Parkinson’s disease and restless legs syndrome, partly enlightening the underlying pathology or the therapeutic efficacy of dopamine agonists to overcome neuronal iron deficiency.

Publisher URL: www.sciencedirect.com/science

DOI: S0006295217307049

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.