The cytotoxicity of dopamine may be an artefact of cell culture.
Administration of L-DOPA is commonly used to treat Parkinson's disease, yet controversy continues as to whether the dopamine arising from it aggravates neuronal loss. Several authors have reported cytotoxic effects of L-DOPA and dopamine on cultured cells, but others have not. In this report using the rat pheochromocytoma cell line PC12 and the M14 human melanoma cell line we show that dopamine-mediated cell death is not specific for neuronal cells. Moreover, our data show that both L-DOPA and dopamine interact with commonly used cell culture media, undergoing oxidation to generate hydrogen peroxide and dopamine semiquinones/quinones. Catalase and reduced glutathione could protect against cytotoxicity. These results suggest that caution needs to be employed when using cell culture studies to predict effects of L-DOPA and/or dopamine in vivo because of the extracellular generation of reactive species in the culture media.
Clement
Marie-Véronique
MV
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Long
Lee Hua
LH
Ramalingam
Jeyakumar
J
Halliwell
Barry
B
D000818:Animals; D016477:Artifacts; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism; D007980:Levodopa / Q000737:chemistry / Q000633:toxicity; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors; D009419:Nerve Tissue Proteins; D016877:Oxidants / Q000032:analysis / Q000096:biosynthesis; D010084:Oxidation-Reduction / Q000187:drug effects; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D003470:Culture Media; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016877:Oxidants; D007980:Levodopa; D006861:Hydrogen Peroxide; D002374:Catalase; D005978:Glutathione; D004298:Dopamine