Chemoprotection against cancer by induction of Phase 2 enzymes
Chemoprotection against cancer by induction of Phase 2 enzymes
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DOI：
10.1002/biof.5520120102
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发表时间：
2000-01-01
期刊：
影响因子：
6
通讯作者：
Talalay, P
中科院分区：
文献类型：
--
作者：
Talalay, P
诱导2相酶是一种有效和充分的策略，可以实现对许多致癌物的毒性和肿瘤效应的保护。建议将第2相酶的概念扩大为只负责功能化外源生物与内源性细胞配体如谷胱甘肽(谷胱甘肽S转移酶)和葡萄糖醛酸基转移酶(UDP葡萄糖醛酸基转移酶)的结合，以包括具有下列共同特征的蛋白质：(A)受各种化学试剂的协调诱导，这些化学试剂都有能力与巯基反应；(B)可能受共同启动子元件的调节；以及(C)通过多种机制催化反应，从而全面保护凝胶和活性氧毒性。这些机制包括：与内源性配体的结合，对可破坏DNA和其他大分子的分子的反应特性的化学修饰，以及细胞抗氧化剂的生成或增强。除了上述结合酶，2相蛋白质的临时和部分列表可能包括：NAD(P)H：苯醌还原酶、环氧化物水解酶、二氢二醇脱氢酶、γ-谷氨酰半胱氨酸合成酶、血红素加氧酶-1、白三烯B1脱氢酶、黄曲霉毒素B-4脱氢酶和铁蛋白。
Induction of Phase 2 enzymes is an effective and sufficient strategy for achieving protection against the toxic and neoplastic effects cf many carcinogens. It is proposed that the concept of Phase 2 enzymes as being responsible only for the conjugation of functionalized xenobiotics with endogenous cellular ligands such as glutathione (glutathione S-transferases) and glucuronic acid (UDP-glucuronosyltransferases) be expanded to include proteins with the following common characteristics: (a) coordinate induction by a broad range of chemical agents that all have the capacity to react with sulfhydryl groups; (b) possible regulation by common promoter elements; and (c) catalysis of reactions that lead to comprehensive protection against electrophile and reactive oxygen toxicities, by a wide variety of mechanisms. These mechanisms include: conjugation with endogenous ligands, chemical modification of reactive features of molecules that can damage DNA and other macromolecules, and generation or augementation of cellular antioxidants. In addition to the above conjugating enzymes, a provisional and partial list of Phase 2 proteins might include: NAD(P)H:quinone reductase, epoxide hydrolase, dihydrodiol dehydrogenase, gamma -glutamylcysteine synthetase, heme oxygenase-1, leukotriene B1 dehydrogenase, aflatoxin B-4 dehydrogenase, and ferritin.