NAD(P)H:Quinone Oxidoreductase (NQO1) Protects Astroglial Cells Against L-Dopa Toxicity
Astroglial cells are well known to protect neurons against the toxicity of L-Dopa, a catecholaminergic drug used in the treatment of Parkinson’s disease (PD) (Han et al., 1996). This observation, together with the abundance of astroglial cells in the brain, has been used to explain the remarkable absence of overt neurotoxicity of L-Dopa in vivo, as opposed to its clear detrimental effect on neuronal survival in vitro (Agid, 1998). The neurotoxicity of L-Dopa in vitro is thought to be caused primarily by its autooxidative breakdown in the presence of molecular oxygen. Under these circumstances, highly unstable Dopa-quinones are formed which induce neuronal damage mainly as a result of the excessive release of reactive oxygen species (ROS), such as superoxide radicals and hydrogen peroxide, during redoxcycling of these compounds (Bindoli et al., 1992). In contrast to neurons, astroglial cells possess a considerable capacity to detoxify ROS. This feature is thought to form a basis both for their relative resistance to oxidative damage and for their neuroprotective potential (Han et al., 1996; Drukarch et al., 1998). Astroglial ROS scavenging capacity depends to a large extent on the presence of high amounts of the thiol anti-oxidant glutathione in these cells. In fact, neuroprotection against L-Dopa toxicity has been associated with the ability of astroglial cells to increase their glutathione content upon exposure to L-Dopa (Han et al., 1996).
KeywordsGlutathione Content Astroglial Cell Quinone Oxidoreductase Quinone Reductase Extracellular Reactive Oxygen Species
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- Chen, S., Wu, K., Zhang, D., Sherman, M., Knox, R., and Yang, C. S., 1999, Molecular characterization ofbinding of substrates and inhibitors to DT-diaphorase: combined approach involving site-directed mutagenesis, inhibitor-binding analysis, and computer modeling, Mol. Pharmacol. 56: 272–278.PubMedGoogle Scholar
- Van Muiswinkel, F. L., Riemers, F. M., Peters, G. J., LaFleur, M. V. M., Siegel, D., Jongenelen, C. A. M., and Drukarch, B., 2000, L-Dopa stimulates expression of the anti-oxidant enzyme NAD(P)H:quinone oxidoreductase (NQO) in cultured astroglial cells, Free Radic. Biol. Med. in press.Google Scholar