Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: Implications in apoptosis
Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: Implications in apoptosis
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DOI：
10.1081/ncn-200027586
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发表时间：
2004-10-01
影响因子：
1.3
通讯作者：
Sasvari-Szekely, M
中科院分区：
文献类型：
--
作者：
Keszler, G;Spasokoukotskaja, T;Sasvari-Szekely, M
脱氧胞苷激酶（dCK），主要的脱氧核苷补救酶的活性的刺激，最近被认为是一种保护性的细胞反应，以广泛的药物干扰DNA修复和凋亡。有鉴于此，dCK激活对细胞凋亡诱导的潜在贡献--可能是通过提供dATP或其类似物来诱导细胞凋亡--值得考虑。人扁桃体淋巴细胞暴露于2-氯-脱氧腺苷（CdA）两小时导致dCK的两倍激活。这种激活过程被pifithrin-alpha（一种有效的p53抑制剂）抑制。当dNTP池进行了测定，脱氧嘧啶三磷酸和dGTP池减少后的治疗，而dATP水平升高62%，77%和50%的CdA，阿非迪霉素和依托泊苷处理的细胞，分别。我们假设，细胞损伤引起的dCK激活可能是一个促凋亡因子，在线粒体释放细胞色素c和脱氧鸟苷激酶之前产生dATP。
Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction-presumably by supplying dATP or its analogues for the apoptosome formation-deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-alpha, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.