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多胺分解代谢:动物抗增殖治疗的靶点和植物应激耐受策略。

Polyamine catabolism: target for antiproliferative therapies in animals and stress tolerance strategies in plants.

机构信息

Department of Biology, University Roma Tre, 00146, Rome, Italy.

出版信息

Amino Acids. 2012 Feb;42(2-3):411-26. doi: 10.1007/s00726-011-1012-1. Epub 2011 Aug 28.

Abstract

Metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, has been a target for antineoplastic therapy since these naturally occurring alkyl amines were found essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. A correlation between regulation of cell proliferation and polyamine metabolism is described. In particular, polyamine catabolism involves copper-containing amine oxidases and FAD-dependent polyamine oxidases. Several studies showed an important role of these enzymes in several developmental and disease-related processes in both animals and plants through a control on polyamine homeostasis in response to normal cellular signals, drug treatment, environmental and/or cellular stressors. The production of toxic aldehydes and reactive oxygen species, H(2)O(2) in particular, by these oxidases using extracellular and intracellular polyamines as substrates, suggests a mechanism by which the oxidases can be exploited as antineoplastic drug targets. This minireview summarizes recent advances on the physiological roles of polyamine catabolism in animals and plants in an attempt to highlight differences and similarities that may contribute to determine in detail the underlined mechanisms involved. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants.

摘要

多胺精脒和精胺及其二胺前体腐胺的代谢一直是抗肿瘤治疗的靶点,因为这些天然存在的烷基胺对于正常哺乳动物细胞的生长是必需的。细胞内多胺浓度通过生物合成、运输和分解代谢的协调和高度调节来维持在细胞类型特异性设定点。描述了细胞增殖和多胺代谢的调节之间的相关性。特别是,多胺分解代谢涉及含铜胺氧化酶和 FAD 依赖性多胺氧化酶。几项研究表明,这些酶在动物和植物的几个发育和与疾病相关的过程中通过控制多胺稳态来响应正常细胞信号、药物治疗、环境和/或细胞应激,从而发挥重要作用。这些氧化酶使用细胞外和细胞内多胺作为底物产生有毒醛和活性氧(特别是 H2O2),这表明氧化酶可以作为抗肿瘤药物靶点的一种机制。这篇综述总结了多胺分解代谢在动物和植物中的生理作用的最新进展,试图突出差异和相似之处,这可能有助于详细确定所涉及的潜在机制。这些信息对于评估该代谢途径作为动物中新型抗增殖治疗和植物中应激耐受策略的靶点的可能性可能是有用的。

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