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Enhancing Effect of Manganese on L‐DOPA‐Induced Apoptosis in PC12 Cells
Author(s) -
Migheli Rossana,
Godani Chiara,
Sciola Luigi,
Delogu Maria R,
Serra Pier Andrea,
Zangani Danilo,
De Natale Guglielmo,
Miele Egidio,
Desole Maria S
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731155.x
Subject(s) - viability assay , apoptosis , oxidative stress , chemistry , tunel assay , metabolite , programmed cell death , microbiology and biotechnology , biochemistry , biology
: L‐DOPA and manganese both induce oxidative stress‐mediated apoptosis in catecholaminergic PC12 cells. In this study, exposure of PC12 cells to 0.2 m M MnCl 2 or 10‐20 μ M L‐DOPA neither affected cell viability, determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, nor induced apoptosis, tested by flow cytometry, fluorescence microscopy, and the TUNEL technique. L‐DOPA (50 μ M ) induced decreases in both cell viability and apoptosis. When 0.2 m M MnCl 2 was associated with 10, 20, or 50 μ M L‐DOPA, a concentration‐dependent decrease in cell viability was observed. Apoptotic cell death also occurred. In addition, manganese inhibited L‐DOPA effects on dopamine (DA) metabolism (i.e., increases in DA and its acidic metabolite levels in both cell lysate and incubation medium). The antioxidant N ‐acetyl‐L‐cysteine significantly inhibited decreases in cell viability, apoptosis, and changes in DA metabolism induced by the manganese association with L‐DOPA. An increase in autoxidation of L‐DOPA and of newly formed DA is suggested as a mechanism of manganese action. These data show that agents that induce oxidative stress‐mediated apoptosis in catecholaminergic cells may act synergistically.