Thymidine phosphorylase inhibits apoptosis induced by cisplatin
Thymidine phosphorylase inhibits apoptosis induced by cisplatin
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DOI：
10.1016/s0006-291x(02)03034-6
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发表时间：
2003-02-07
影响因子：
3.1
通讯作者：
Akiyama, S
中科院分区：
文献类型：
--
作者：
Ikeda, R;Furukawa, T;Akiyama, S
血小板源性内皮细胞生长因子/胸苷磷酸化酶（PD-ECGF/TP）是一种血管生成因子，可刺激内皮细胞的趋化性，并对缺氧诱导的细胞凋亡具有抵抗作用。2-脱氧核糖（2- deoxy - d -核糖）是TP产生的胸腺嘧啶降解产物，部分阻止缺氧诱导的细胞凋亡。在多种人类癌中，TP在肿瘤组织中的表达水平高于邻近的非肿瘤组织。TP的高表达与不良预后相关。为了研究TP对顺铂诱导的人白血病Jurkat细胞凋亡的影响，我们转染了野生型或突变型（L148R） TP cDNA。TP抑制顺铂诱导的凋亡通路中的多个步骤，半胱天冬酶3和9的激活以及线粒体细胞色素c的释放。这些发现提示了TP抵抗顺铂诱导的细胞凋亡的机制。此外，没有酶活性的TP突变体也抑制顺铂诱导的细胞凋亡。这些结果表明，TP具有不依赖于其酶活性的细胞保护作用。(C) 2003 Elsevier Science（美国）版权所有。
An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-DeOXY-D-ribose, a degradation product of thymidine generated by TP, partially prevents hypoxia-induced apoptosis. TP is expressed at higher levels in tumor tissues compared to the adjacent non-neoplastic tissues in a variety of human carcinomas. High expression of TP is associated with an unfavorable prognosis. To investigate the effect of TP on cisplatin-induced apoptosis, human leukemia Jurkat cells were transfected with wildtype or mutant (L148R) TP cDNA. TP inhibited a number of steps in the cisplatin-induced apoptotic pathway, activation of caspases 3 and 9 and mitochondrial cytochrome c release. These findings suggest a mechanism by which TP confers resistance to apoptosis induced by cisplatin. Moreover, mutant TP that has no enzymatic activity also suppressed cisplatin-induced apoptosis. These findings indicate that TP has cytoprotective functions against cytotoxic agents which are independent of its enzymatic activity. (C) 2003 Elsevier Science (USA). All rights reserved.