Nitric oxide and dihydrolipoic acid modulate the activity of caspase 3 in HepG2 cells.
Herein, we report that dihydrolipoic acid and lipoic acid (LA) plus lipoamide dehydrogenase and NADH denitrosate S-nitrosocaspase 3 (CASP-SNO). In HepG2 cells, S-nitroso-L-cysteine ethyl ester (SNCEE) impeded the activity of caspase 3 (CASP-SH), while a subsequent incubation of the cells in SNCEE-free medium resulted in endogenous denitrosation and reactivation of CASP-SH. The latter process was inhibited in thioredoxin reductase-deficient HepG2 cells, in which, however, LA markedly reactivated CASP-SH. The data obtained are discussed with focus on low molecular mass dithiols that mimic the activity of thioredoxin in reactions of protein S-denitrosation.
Sengupta
Rajib
R
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Billiar
Timothy R
TR
Atkins
James L
JL
Kagan
Valerian E
VE
Stoyanovsky
Detcho A
DA
D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000172:deficiency
D009569:Nitric Oxide; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D013880:Thioredoxin-Disulfide Reductase; D053148:Caspase 3