Docampo R, Moreno S N, Mason R P
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709.
Chem Biol Interact. 1988;65(2):123-31. doi: 10.1016/0009-2797(88)90049-x.
5-(4-Nitrophenyl)penta-2,4-dienal (NPPD) stimulated NADPH-supported oxygen consumption by rat liver microsomes in a concentration-dependent manner. The NPPD stimulation of O2 uptake was not inhibited by metyrapone and was decreased in the presence of NADP+ and p-hydroxymercuribenzoate. These observations suggest that the NPPD initial reduction step is mediated by NADPH-cytochrome P-450 reductase and not by cytochrome P-450. Spin-trapping studies using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the formation of superoxide anion upon incubation of NPPD, NADPH, DMPO and rat liver microsomes. Hydrogen peroxide generation was also detected in these incubations, thus confirming redox cycling of NPPD under aerobic conditions. NPPD stimulated oxygen consumption, superoxide anion formation and hydrogen peroxide generation by rat kidney, testes and brain microsomes. Other enzymes capable of nitroreduction (NADH dehydrogenase, xanthine oxidase, glutathione reductase, and NADP+ ferredoxin oxidoreductase) were also found to stimulate redox cycling of NPPD. The ability of NPPD to induce superoxide anion and hydrogen peroxide formation might play a role in its reported mutagenicity.
5-(4-硝基苯基)-2,4-戊二烯醛（NPPD）以浓度依赖性方式刺激大鼠肝脏微粒体中由NADPH支持的氧消耗。NPPD对氧摄取的刺激不受甲吡酮抑制，且在存在NADP+和对羟基汞苯甲酸时降低。这些观察结果表明，NPPD的初始还原步骤由NADPH-细胞色素P-450还原酶介导，而非细胞色素P-450。使用5,5-二甲基-1-吡咯啉N-氧化物（DMPO）的自旋捕获研究表明，在NPPD、NADPH、DMPO与大鼠肝脏微粒体一起孵育时会形成超氧阴离子。在这些孵育中还检测到过氧化氢的产生，从而证实了NPPD在有氧条件下的氧化还原循环。NPPD刺激大鼠肾脏、睾丸和脑微粒体的氧消耗、超氧阴离子形成和过氧化氢产生。还发现其他能够进行硝基还原的酶（NADH脱氢酶、黄嘌呤氧化酶、谷胱甘肽还原酶和NADP+铁氧化还原蛋白氧化还原酶）也能刺激NPPD的氧化还原循环。NPPD诱导超氧阴离子和过氧化氢形成的能力可能在其已报道的致突变性中起作用。
