Ta. Sarafian et al., BCL-2 EXPRESSION DECREASES METHYL MERCURY-INDUCED FREE-RADICAL GENERATION AND CELL-KILLING IN A NEURAL CELL-LINE, Toxicology letters, 74(2), 1994, pp. 149-155
Methyl mercury neurotoxicity is associated with a broad range of neuro
pathologic and biochemical disturbances which include induction of oxi
dative injury. Treatment of the hypothalamic neural cell line GT1-7 wi
th 10 mu M methyl mercury (MeHg) for 3 h resulted in increased formati
on of reactive oxygen species (ROS), and decreased levels of reduced g
lutathione (GSH), associated with 20% cell death. Cells transfected wi
th an expression construct for the anti-apoptotic proto-oncogene, bcl-
2, displayed attenuated ROS induction and negligible cell death. Twent
y-four-h exposure to 5 mu M MeHg killed 56% of control cells, but only
19% of bcl-2-transfected cells. By using diethyl maleate to deplete c
ells of GSH, we demonstrate that the differential sensitivity to MeHg
was not due solely to intrinsically different GSH levels. The data sug
gest that MeHg-mediated cell killing correlates more closely with ROS
generation than with GSH levels and that bcl-2 protects MeHg-treated c
ells by suppressing ROS generation.