Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or both?
Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or both?
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DOI：
10.1093/jb/mvj021
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发表时间：
2006
影响因子：
2.7
通讯作者：
Yanlin Wang;R. Casero
中科院分区：
文献类型：
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作者：
Yanlin Wang;R. Casero
随着多胺分解代谢酶精胺氧化酶（SMO/PAOh 1）的发现，多胺代谢途径的复杂性大大增加。单独或与人类多胺分解代谢的另外两个已知成员亚精胺/精胺N（1）-乙酰基转移酶和N（1）-乙酰多胺氧化酶（PAO）组合，SMO/PAOh 1表达有可能改变多胺稳态以响应正常细胞信号、药物治疗和环境和/或细胞应激源。产生有毒醛和活性氧（ROS）H（2）O（2）的氧化酶的活性表明，这些氧化酶可以作为药物靶点。然而，通路的不适当激活也可能导致病理结果，包括可能导致细胞转化的DNA损伤。最新的数据表明，这两个多胺分解代谢途径表现出不同的性能和了解这些性能应有助于他们的开发治疗和/或化学预防策略。
With the recent discovery of the polyamine catabolic enzyme spermine oxidase (SMO/PAOh1), the apparent complexity of the polyamine metabolic pathway has increased considerably. Alone or in combination with the two other known members of human polyamine catabolism, spermidine/spermine N(1)-acetyltransferase, and N(1)-acetylpolyamine oxidase (PAO), SMO/PAOh1 expression has the potential to alter polyamine homeostasis in response to normal cellular signals, drug treatment and environmental and/or cellular stressors. The activity of the oxidases producing toxic aldehydes and the reactive oxygen species (ROS) H(2)O(2), suggest a mechanism by which these oxidases can be exploited as an antineoplastic drug target. However, inappropriate activation of the pathways may also lead to pathological outcomes, including DNA damage that can lead to cellular transformation. The most recent data suggest that the two polyamine catabolic pathways exhibit distinct properties and understanding these properties should aid in their exploitation for therapeutic and/or chemopreventive strategies.