BCL-2 EXPRESSION DECREASES METHYL MERCURY-INDUCED FREE-RADICAL GENERATION AND CELL-KILLING IN A NEURAL CELL-LINE

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.