title: DT-diaphorase protects astrocytes from aminochrome-induced toxicity.
abstract: 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.
authors.affiliation: Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Chile.
authors.forename: Sandro
authors.initials: S
authors.lastname: Huenchuguala
authors.affiliation: Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Chile.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Graumann
authors.affiliation: Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Chile.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Paris
authors.affiliation: Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Chile. Electronic address: jsegura@med.uchile.cl.
authors.forename: Juan
authors.initials: J
authors.lastname: Segura-Aguilar
mesh_terms: D001253:Astrocytes / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D001728:Dicumarol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D045563:Indolequinones / Q000633:toxicity*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D045563:Indolequinones; D034741:RNA, Small Interfering; C091584:aminochrome 1; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2
keywords: Aminochrome; Dicoumarol; Dopamine; Glutathione transferase; Neuromelanin