Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3
Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3
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DOI：
10.1016/j.bbrc.2008.03.067
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发表时间：
2008-05-30
影响因子：
3.1
通讯作者：
Yamadaa, Katsushi
中科院分区：
文献类型：
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作者：
Ikeda, Ryuji;Tajitsu, Yusuke;Yamadaa, Katsushi
胸苷磷酸化酶(TP)是一种血管生成因子，对缺氧诱导的细胞凋亡具有抵抗作用。我们利用转染TP基因的Jurkat细胞Jurkat/TP和模拟细胞Jurkat/CV，研究了TP抑制低氧诱导的细胞凋亡的分子基础。TP和TP酶活性产生的胸苷降解产物2-脱氧-D-核糖可抑制缺氧诱导的细胞凋亡。它们还能抑制缺氧诱导的缺氧诱导因子1α的上调以及促凋亡因子BNIP3和caspase 3的激活。在Jurkat细胞中引入针对BNIP3的siRNA可降低缺氧条件下细胞的凋亡率。这些发现表明，茶多酚抑制BNIP3的表达至少部分地阻止了缺氧诱导的细胞凋亡。在许多恶性实体肿瘤中，TP的表达水平升高，因此，TP在这些肿瘤中产生的2-脱氧-D-核糖可能通过阻止缺氧诱导的细胞凋亡而在肿瘤的进展中发挥重要作用。(C)2008 Elsevier Inc.保留所有权利。
An angiogenic factor, thymidine phosphorylase (TP), confers resistance to apoptosis induced by hypoxia. We investigated the molecular basis for the suppressive effect of TP on hypoxia-induced apoptosis using Jurkat cells transfected with TP cDNA, Jurkat/TP, and a mock transfectant, Jurkat/CV. TP and 2-deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, suppressed hypoxia-induced apoptosis. They also inhibited the upregulation of hypoxia-inducible factor (HIF) 1 alpha and the proapoptotic factor, BNIP3, and caspase 3 activation induced by hypoxia. Introduction of siRNA against BNIP3 in Jurkat cells decreased the proportion of apoptotic cells under hypoxic condition. These findings suggest that the suppression of BNIP3 expression by TP prevents, at least in part, hypoxia-induced apoptosis. Expression levels of TP are elevated in many malignant solid tumors and thus 2-deoxy-D-ribose generated by TP in these tumors might play an important role in tumor progression by preventing hypoxia-induced apoptosis. (C) 2008 Elsevier Inc. All rights reserved.