Cellular effects of dopamine--beyond oxidative mechanisms.
Cell cycle blockers inhibit growth in dividing cells, but promote survival of differentiated cells, including neurons. Low micromolar dopamine profoundly inhibited cell growth in dopamine transporter transfected SK-N-MC neuroblastoma cells by cell cycle arrest at G(1). This effect was independent of oxy radical formation, antagonized by transporter block, abolished by FeCl(3) and mimicked by the iron chelator deferoxamine. We propose that dopamine inhibits cell growth by its ability to chelate intracellular iron. This novel biological action unrelated to neurotransmitter receptors, second messengers or oxidative stress, observed in human neuroblastoma cells of striatal origin, may be important for cell differentiation during neurodevelopment and survival of differentiated dopamine (nigral) neurons.
Pifl
Christian
C
Brain Research Institute, University of Vienna, Spitalgasse 4, 1090, Vienna, Austria. christian.pifl@univie.ac.at
Kattinger
Alexandra
A
Reither
Harald
H
Hornykiewicz
Oleh
O
D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016877:Oxidants; D004298:Dopamine