PMID- 29208364
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20220119
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 148
DP  - 2018 Feb
TI  - Dopamine promotes cellular iron accumulation and oxidative stress responses in 
      macrophages.
PG  - 193-201
LID - S0006-2952(17)30704-9 [pii]
LID - 10.1016/j.bcp.2017.12.001 [doi]
AB  - 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-1alpha. 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.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Dichtl, Stefanie
AU  - Dichtl S
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria.
FAU - Haschka, David
AU  - Haschka D
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria.
FAU - Nairz, Manfred
AU  - Nairz M
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria.
FAU - Seifert, Markus
AU  - Seifert M
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria.
FAU - Volani, Chiara
AU  - Volani C
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria.
FAU - Lutz, Oliver
AU  - Lutz O
AD  - Austrian Drug Screening Institute (ADSI), Innsbruck, Austria.
FAU - Weiss, Gunter
AU  - Weiss G
AD  - Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology 
      and Pneumology), Medical University of Innsbruck, A-6020 Innsbruck, Austria. 
      Electronic address: guenter.weiss@i-med.ac.at.
LA  - eng
GR  - W 1253/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171205
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 42HK56048U (Tyrosine)
RN  - E1UOL152H7 (Iron)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Cells, Cultured
MH  - Dopamine/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Iron/*metabolism
MH  - Macrophages/*drug effects/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Norepinephrine/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Tyrosine/pharmacology
OTO - NOTNLM
OT  - Catecholamine
OT  - Dopamine
OT  - Iron
OT  - Macrophage
OT  - Oxidative stress
EDAT- 2017/12/07 06:00
MHDA- 2018/12/18 06:00
CRDT- 2017/12/07 06:00
PHST- 2017/09/15 00:00 [received]
PHST- 2017/12/01 00:00 [accepted]
PHST- 2017/12/07 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2017/12/07 06:00 [entrez]
AID - S0006-2952(17)30704-9 [pii]
AID - 10.1016/j.bcp.2017.12.001 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2018 Feb;148:193-201. doi: 10.1016/j.bcp.2017.12.001. Epub 
      2017 Dec 5.