Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis
Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis
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DOI：
10.1023/a:1006960126369
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发表时间：
1999-03-01
影响因子：
4.3
通讯作者：
Huang, AC
中科院分区：
文献类型：
--
作者：
Jacobson, EL;Shieh, WM;Huang, AC
这里提出的研究表明，细胞NAD，我们假设是烟酸状态的相关生物标志物，是显着低于在人类比通常研究的动物模型的致癌作用。我们表明，烟酰胺和由此产生的细胞NAD浓度调节肿瘤抑制蛋白，p53，在人类乳腺，皮肤和肺细胞的表达。确定乳腺上皮细胞中响应DNA损伤的最佳NAD浓度的研究表明，DNA损伤似乎刺激NAD生物合成，并且在较高NAD存在下或在经历活性NAD生物合成的细胞中，DNA损伤的恢复提前数小时发生。最后，对来自诊断患有光化性角化病或鳞状细胞癌的个体的正常人皮肤组织的分析表明，皮肤的NAD含量与恶性表型呈负相关。由于NAD在调节ADP-核糖聚合物代谢、环状ADP-核糖合成中是重要的。和应激反应蛋白，如p53，在DNA损伤后，了解NAD代谢是如何在人体内调节，在发展预防和治疗癌症的策略具有重要意义。
Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis. We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells. Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis. Finally, analyses of normal human skin tissue from individuals diagnosed with actinic keratoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype. Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis. and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis.