期刊
NEUROTOXICOLOGY
卷 55, 期 -, 页码 10-12出版社
ELSEVIER
DOI: 10.1016/j.neuro.2016.04.014
关键词
Dopamine; Glutathione transferase; Aminochrome; Neuromelanin; Dicoumarol
资金
- FONDECYT [1100165]
- University of Chile [ENL014/14]
Astrocytes are exposed to aminochrome via the oxidation of dopamine that is taken up from the synaptic cleft after its release from dopaminergic neurons. Glutathione transferase M2-2 (GSTM2) has been shown to protect astrocytes from aminochrome-induced toxicity, but astrocytes also express DT-diaphorase, which has been shown to prevent aminochrome-induced neurotoxicity in dopaminergic neurons. Therefore, the question is whether DT-diaphorase also protects astrocytes from aminochrome-induced toxicity. DT-diaphorase is constitutively expressed in U373MG cells, and its inhibition by dicoumarol induced a significant increase of aminochrome-induced cell death. However, the inhibition of DT-diaphorase in U373MGsiGST6 cells, which have 74% of GSTM2 gene expression silenced, resulted in a more than 2-fold increase in cell death, suggesting that DT-diaphorase plays an important role in preventing aminochrome-induced toxicity in astrocytes. (C) 2016 Elsevier B.V. All rights reserved.
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