Inflammation and polyamine catabolism: the good, the bad and the ugly
Inflammation and polyamine catabolism: the good, the bad and the ugly
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DOI：
10.1042/bst0350300
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发表时间：
2007-04-01
影响因子：
3.9
通讯作者：
Casero, R. A., Jr.
中科院分区：
文献类型：
--
作者：
Babbar, N.;Murray-Stewart, T.;Casero, R. A., Jr.
通过特异性抗肿瘤多胺类似物诱导多胺催化剂，增加了对多胺催化剂在细胞生长、死亡和对各种抗肿瘤剂的反应中所起作用的兴趣。除了两步亚精胺/精胺N-1-乙酰转移酶（SSAT）/N-1-乙酰多胺氧化酶（APAO）分解代谢途径外，最近发现的一种可诱导的哺乳动物精胺氧化酶（SMO/PAOh 1）强调了多种刺激物对多胺催化剂调节的复杂性。此外，最近的数据表明，感染因子和炎症介质也可以上调多胺催化剂。通过这些试剂诱导SSAT可以降低细胞内多胺浓度和细胞生长速率，从而提供细胞可以适应炎症应激的有益机制。然而，增加的多胺催化剂也可通过产生作为APAO或SMO/PAOh 1活性的副产物的H2 O2而导致细胞内活性氧（ROS）的显著增加。这种增加的ROS生成可以具有不同的结果，这取决于诱导机制和所涉及的细胞类型。通过刺激SSAT/APAO和/或SMO/PAOh 1的试剂靶向杀死肿瘤细胞显然是“良好”的效果。然而，通过炎症或感染因子诱导SMO/PAOh 1有可能在正常的非肿瘤细胞中产生足够的ROS，导致DNA损伤、突变和潜在的致癌转化（“坏”）。这些多胺分解代谢酶的诱导的变化，以及这种诱导的水平和时机将决定在期望和不期望的效果（“丑陋”）存在下的细胞结果。在这里，我们讨论的相对作用，每一个步骤的多胺催化剂在炎症应激反应。
The induction of polyamine catabolism by specific anti-tumour polyamine analogues has increased interest in the roles polyamine catabolism play in cell growth, death and response to various anti-tumour agents. The relatively recent finding of an inducible mammalian spermine oxidase (SMO/PAOh1), in addition to the two-step spermidine/spermine N-1-acetyltransferanse (SSAT)/N-1-acetylpolyamine oxidase (APAO) catabolic pathway, underscores the complexities of the regulation of polyamine catabolism by various stimuli. Furthermore, recent data indicate that infectious agents and mediators of inflammation can also up-regulate polyamine catabolism. Induction of SSAT by these agents can reduce intracellular polyamine concentrations and cell growth rate, thus providing a beneficial mechanism by which cells may adapt to inflammatory stress. However, increased polyamine catabolism can also result in substantial increases in intracellular reactive oxygen species (ROS) through the production of H2O2 as a by-product of either APAO or SMO/PAOh1 activity. This increased generation of ROS can have different results, depending on the mechanism of induction and cell types involved. Targeted killing of tumour cells by agents that stimulate SSAT/APAO and/or SMO/PAOh1 is obviously a 'good' effect. However, induction of SMO/PAOh1 by inflammation or infectious agents has the potential to produce sufficient ROS in normal, non-tumour cells to lead to DNA damage, mutation and, potentially, carcinogenic transformation ('bad'). The variation in the induction of these polyamine catabolic enzymes, as well as the level and timing of this induction will dictate the cellular outcome in the presence of both desirable and undesirable effects ('ugly'). Here we discuss the relative role of each of the steps in polyamine catabolism in response to inflammatory stress.