期刊
JOURNAL OF NEURAL TRANSMISSION
卷 114, 期 7, 页码 909-918出版社
SPRINGER WIEN
DOI: 10.1007/s00702-006-0622-3
关键词
apoptosis; beta-carboline; caspase 3; dopamine melanin; grp78; hsp90; neuromelanin; norharman; pigment
ne 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 PC 12 cells. Dopamine melanin protected against norharman-induced upregulation of grp78, activation of caspase 3 and necrosis at low concentrations (5 and 50 mu M). In contrast, at a high conentration (500 mu M) 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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