Antioxidants protect against dopamine-induced metallothionein-III (GIF) mRNA expression in mouse glial cell line (VR-2g)

Metallothionein (MT)-III, originally discovered as a growth inhibitory fact or (GIF), is a brain specific isomer of MTs and is markedly reduced in the brain of patients with Alzheimer's disease (AD) or other neurodegenerative diseases. We analyzed the level and regulation of mRNA expression of MT-III in immortalized fetal mouse brain glial cells (VR-2g) by reverse transcrip tase-polymerase chain reaction (RT-PCR). We have recently reported that dop amine (DA) increases the expression of MT-III mRNA in vitro. In this study, we investigated the mechanism of such increase by examining the effects of DA agonists (SKF38393 or bromocriptine) and DA antagonists (SCH23390 or su lpiride) on the expression of MT-III mRNA. MT-III mRNA did not change by ei ther agonist and DA-increased MT-III mRNA was not inhibited by either antag onist. These results suggested that the induction of MT-III mRNA by DA was not mediated by stimulation of DA receptors. On the other hand, DA-induced MT-III mRNA expression was strongly inhibited by the addition of antioxidan ts (glutathione, vitamin E or ascorbic acid), indicating thar DA-enhanced M T-III mRNA was mediated by reactive oxygen species. Our results suggest tha t oxidative stress may be one of the principle factors that modulate MT-III mRNA expression. (C) 2000 Elsevier Science B.V. All rights reserved.