Differential effects of human neuromelanin and synthetic dopamine melanin on neuronal and glial cells.
We investigated the effects of neuromelanin (NM) isolated from the human substantia nigra and synthetic dopamine melanin (DAM) on neuronal and glial cell lines and on primary rat mesencephalic cultures. Lactate dehydrogenase (LDH) activity and lipid peroxidation were significantly increased in SK-N-SH cells by DAM but not by NM. In contrast, iron-saturated NM significantly increased LDH activity in SK-N-SH cells, compared with 100 mg/mL ETDA-treated NM containing a low concentration of bound iron. DAM, but not NM, stimulated hydroxyl radical production and increased SK-N-SH cell death via apoptotic-like mechanisms. Neither DAM nor NM induced any changes in the glial cell line U373. 3H-dopamine uptake in primary rat mesencephalic cultures was significantly reduced in DAM-compared with NM-treated cultures, accompanied by increased cell death via an apoptosis-like mechanism. Interestingly, Fenton-induced cell death was significantly decreased in cultures treated with both Fenton reagent and NM, an effect not seen in cultures treated with Fenton reagent plus DAM. These data are suggestive of a protective role for neuromelanin under conditions of high oxidative load. Our findings provide new evidence for a physiological role for neuromelanin in vivo and highlights the caution with which data based upon model systems should be interpreted.
Li
Jie
J
Clinical Neurochemistry and National Parkinson Foundation Center of Excellence Laboratories, Clinic and Policlinic for Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany.
Scheller
Carsten
C
Koutsilieri
Eleni
E
Griffiths
Francine
F
Beart
Philip M
PM
Mercer
Linda D
LD
Halliday
Glenda
G
Kettle
Emma
E
Rowe
Dominic
D
Riederer
Peter
P
Gerlach
Manfred
M
Rodriguez
Michael
M
Double
Kay L
KL
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008543:Melanins / Q000494:pharmacology*; D008854:Microscopy, Electron; D009457:Neuroglia / Q000187:drug effects* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008543:Melanins; C081789:dopamine melanin; C014121:neuromelanin; D017665:Hydroxyl Radical; D007770:L-Lactate Dehydrogenase; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine