Nitric oxide and thioredoxin type 1 modulate the activity of caspase 8 in HepG2 cells.
Herein, we report that nitric oxide (NO) and the thioredoxin/thioredoxin reductase system affect the activity of caspase 8 in HepG2 cells. Exposure of cells to NO resulted in inhibition of caspase 8, while a subsequent incubation of the cells in NO-free medium resulted in spontaneous reactivation of the protease. The latter process was inhibited in thioredoxin reductase-deficient HepG2 cells, in which, however, lipoic acid markedly reactivated caspase 8. The data obtained suggest that extrinsic apoptosis can be subjected to redox regulation before induction of proteolytic damage by caspase 3.
Sengupta
Rajib
R
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Billiar
Timothy R
TR
Kagan
Valerian E
VE
Stoyanovsky
Detcho A
DA
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D008063:Thioctic Acid / Q000378:metabolism / Q000494:pharmacology; D054481:Thioredoxin Reductase 1 / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D061945:Caspase Inhibitors; D011500:Protein Synthesis Inhibitors; C491203:TXN protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013879:Thioredoxins; D008063:Thioctic Acid; D003513:Cycloheximide; D054481:Thioredoxin Reductase 1; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8