Nemeikaite-Ceniene Ausra, Dringeliene Aldona, Sarlauskas Jonas, Cenas Narimantas
Institute of Immunology of Vilnius University, Vilnius, Lithuania.
Acta Biochim Pol. 2005;52(4):937-41. Epub 2005 Jun 6.
We aimed to characterize the role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by antitumour quinones RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) and MeDZQ (2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone). Digitonin-permeabilized FLK cells catalyzed NADPH-dependent single- and two-electron reduction of RH1 and MeDZQ. At equitoxic concentrations, RH1 and MeDZQ induced apoptosis more efficiently than the nonalkylating duroquinone or H(2)O(2). The antioxidant N,N'-diphenyl-p-phenylene diamine, desferrioxamine, and the inhibitor of NQO1 dicumarol, protected against apoptosis induction by all compounds investigated, but to a different extent. The results of multiparameter regression analysis indicate that RH1 and MeDZQ most likely induce apoptosis via NQO1-linked formation of alkylating species but not via NQO1-linked redox cycling.
我们旨在阐明NAD(P)H:醌氧化还原酶（NQO1）在抗肿瘤醌类化合物RH1（2,5-二叠氮基-3-羟甲基-6-甲基-1,4-苯醌）和MeDZQ（2,5-二甲基-3,6-二叠氮基-1,4-苯醌）诱导细胞凋亡过程中的作用。用洋地黄皂苷通透处理的FLK细胞催化了RH1和MeDZQ的NADPH依赖性单电子和双电子还原反应。在等毒性浓度下，RH1和MeDZQ比非烷基化的杜醌或H₂O₂更有效地诱导细胞凋亡。抗氧化剂N,N'-二苯基对苯二胺、去铁胺以及NQO1抑制剂双香豆素，对所研究的所有化合物诱导的细胞凋亡均有保护作用，但程度不同。多参数回归分析结果表明，RH1和MeDZQ最有可能通过NQO1连接形成烷基化物质来诱导细胞凋亡，而不是通过NQO1连接的氧化还原循环。
