Differential effects of dopamine melanin on norharman-induced toxicity in PC12 cells
2007 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 114, no 7, 909-918 p.Article in journal (Refereed) Published
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 and a disassociation of melanin aggregates and dispersal of melanin 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.
Place, publisher, year, edition, pages
2007. Vol. 114, no 7, 909-918 p.
apoptosis, b-carboline, caspase 3, dopamine melanin, grp78, hsp90, neuromelanin, norharman, pigment
Pharmacology and Toxicology
Research subject Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-93506DOI: 10.1007/s00702-006-0622-3ISI: 000248001800006OAI: oai:DiVA.org:uu-93506DiVA: diva2:167000