NDLI: Dopamine as a Potent Inducer of Cellular Glutathione and NAD(P)H:Quinone Oxidoreductase 1 in PC12 Neuronal Cells: A Potential Adaptive Mechanism for Dopaminergic Neuroprotection

Content Provider	Springer Nature Link
Author	Jia, Zhenquan Zhu, Hong Misra, Bhaba R. Li, Yunbo Misra, Hara P.
Copyright Year	2008
Abstract	Dopamine auto-oxidation and the consequent formation of reactive oxygen species and electrophilic quinone molecules have been implicated in dopaminergic neuronal cell death in Parkinson’s disease. We reported here that in PC12 dopaminergic neuronal cells dopamine at noncytotoxic concentrations (50–150 μM) potently induced cellular glutathione (GSH) and the phase 2 enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), two critical cellular defenses in detoxification of ROS and electrophilic quinone molecules. Incubation of PC12 cells with dopamine also led to a marked increase in the mRNA levels for γ-glutamylcysteine ligase catalytic subunit (GCLC) and NQO1. In addition, treatment of PC12 cells with dopamine resulted in a significant elevation of GSH content in the mitochondrial compartment. To determine whether treatment with dopamine at noncytotoxic concentrations, which upregulated the cellular defenses could protect the neuronal cells against subsequent lethal oxidative and electrophilic injury, PC12 cells were pretreated with dopamine (150 μM) for 24 h and then exposed to various cytotoxic concentrations of dopamine or 6-hydroxydopamine (6-OHDA). We found that pretreatment of PC12 cells with dopamine at a noncytotoxic concentration led to a remarkable protection against cytotoxicity caused by dopamine or 6-OHDA at lethal concentrations, as detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium reduction assay. In view of the critical roles of GSH and NQO1 in protecting against dopaminergic neuron degeneration, the above findings implicate that upregulation of both GSH and NQO1 by dopamine at noncytotoxic concentrations may serve as an important adaptive mechanism for dopaminergic neuroprotection.
Starting Page	2197
Ending Page	2205
Page Count	9
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	33
Issue Number	11
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2008-03-27
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Glutathione NAD(P)H:quinone oxidoreductase 1 Dopamine 6-Hydroxydopamine PC12 cells Cytotoxicity Neurology Biochemistry Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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