The role of oxidative stress in neuromelanin synthesis in PC12 cells

• Published in: Neuroscience 2011-08, Vol.189, p.43-50
• Main Authors: He, A.-Y, Qiu, L.-J, Gao, Y, Zhu, Y, Xu, Z.-W, Xu, J.-M, Zhang, Z.-H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Survival; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Glucose Oxidase - pharmacology; levodopa; Levodopa - pharmacology; Medical sciences; Melanins - biosynthesis; Neurology; neuromelanin; Oxidative Stress; Parkinson's disease; PC12 Cells; Rats; Reactive Oxygen Species - metabolism; Tyrosine 3-Monooxygenase - metabolism; tyrosine hydroxylase; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.05.040

Abstract Previous research has indicated that neuromelanin (NM) is involved in the pathogenesis of Parkinson's disease (PD). Increased reactive oxygen species (ROS) generation in PD sufferers is thought to be related to enhanced tyrosine hydroxylase (TH) activity and NM production. However, few reports have confirmed this hypothesis. In this study, PC12 cells of all experiments were exposed to 50 μmol/L levodopa ( l -DOPA) to generate a model for NM synthesis. Meanwhile, PC12 cells were treated with glucose oxidase (GO) at different concentrations to generate oxidative stress. Finally, cell viability, TH activity, and NM generation in PC12 cells were measured. The results showed that GO dose-dependently stimulated oxidative stress generation in PC12 cells. Moderate increases in oxidative stress enhanced the viability of PC12 cells. However, an excessive level of oxidative stress can lead to the degeneration of PC12 cells. Notably, in the surviving PC12 cells, ROS significantly increased the TH activity, and the NM production was also upregulated. Thus, oxidative stress may upregulate the synthesis of NM, which may be a result of the increased TH activity observed in response to the elevated ROS in l -DOPA-treated PC12 cells.