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Differential effects of dopamine melanin on norharman-induced toxicity in PC12 cells

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Summary

The food contaminant norharman structurally resembles MPTP a compound that selectively damages pigmented brain areas. Both compounds are sequestered and retained in melanin-containing neurons. The aim of the study was to examine whether intracellular melanin can modulate the toxicity of norharman in melanin-loaded PC12 cells. Dopamine melanin protected against norharman-induced upregulation of grp78, activation of caspase 3 and necrosis at low concentrations (5 and 50 µM). In contrast, at a high conentration (500 µM) there was a significantly increased expression of grp78, hsp90 and caspase 3 and a disassociation of melanin aggregates leading to dispersal of granules to swollen neurite terminals. In human populations, a long-term low-level exposure to toxicants with a high affinity to melanin will probably result in accumulation in melanin-containing neurons in vivo. Our data suggest that accumulation of a neurotoxicant in melanin-loaded cells may lead to increased cell stress, apoptotic signaling and disassociation of melanin aggregates.

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  1. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

    A. Östergren, N. G. Lindquist & E. B. Brittebo

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Östergren, A., Lindquist, N. & Brittebo, E. Differential effects of dopamine melanin on norharman-induced toxicity in PC12 cells. J Neural Transm 114, 909–918 (2007). https://doi.org/10.1007/s00702-006-0622-3

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