Fig. 5.

BVR and glutathione (GSH) pathways, respectively, protect against oxidants that differentially target lipids and protein. (A) Depletion of BVR enhances hydrogen peroxide (H₂O₂)-induced cell death greater than glutathione depletion. HEK293 cells were transfected with the BVR or control siRNA, then treated with 1 mM BSO at 48 h to deplete glutathione. At 72 h posttransfection, cells were treated for 14 h with 500 μM H₂O₂ and cell death was determined by MTT assay. BVR depleted cells exhibit markedly increased cell death compared to GSH-depleted cells. (B) Greater protection against 6-hydroxydopamine (6-OH DA)-induced cell death is provided by the GSH pathway than the bilirubin pathway. Cells were depleted of BVR and GSH as in A, then treated 14 h with 300 μM 6-OH DA. Cell death is greater following depletion of GSH than BVR. Data are means of triplicates from at least 3 independent experiments. *, P < 0.05 by t test.