Enhanced toxicity to the catecholamine tyramine in polyglutamine transfected SH-SY5Y cells.
Huntington's disease (HD) is a progressive neurodegenerative disorder, of which the pathogenesis is not completely understood. In patients with Huntington's disease, there is a mutation in the gene encoding the protein huntingtin, which results in an expanded polyglutamine sequence leading to degeneration of the basal ganglia. There is mounting evidence that metabolism of the transmitter dopamine by the enzyme monoamine oxidase may contribute to striatal damage in mitochondrial toxin-induced models of HD. In this study, we have examined the role of the catecholamine tyramine in neural SH-SY5Y cells transfected with normal and expanded polyglutamine repeat numbers. Our findings demonstrate that cells containing a pathological number of polyglutamines are more sensitive to tyramine than cells with a non-pathological number. Tyramine-induced cell death was attenuated by MAO inhibitors as well as with catalase and the iron chelator deferoxamine, suggesting that H202 might mediate the observed toxicity. These observations support the notion that the metabolism of dopamine plays a role in neuron death in Huntington's disease.
Smith
Rebecca R
RR
Department of Neurology, University of Kentucky, Lexington, KY 40536-0284, USA.
Dimayuga
Edgardo R
ER
Keller
Jeffrey N
JN
Maragos
William F
WF
D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010455:Peptides / Q000235:genetics*; D014162:Transfection; D014439:Tyramine / Q000633:toxicity*
D007502:Iron Chelating Agents; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010455:Peptides; C097188:polyglutamine; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D008995:Monoamine Oxidase; D003676:Deferoxamine; D004298:Dopamine; D014439:Tyramine