Szondy Z
Department of Biochemistry, University Medical School of Debrecen, Hungary.
Biochem J. 1995 Oct 15;311 ( Pt 2)(Pt 2):585-8. doi: 10.1042/bj3110585.
2-chloroadenosine induced DNA fragmentation and cell death in human thymocytes primarily by Ca(2+)-dependent mechanisms. Incubation of human thymocytes with 2-chlorodeoxyadenosine (5-1000 nM) also induced cell death (apoptosis) which was dependent on macromolecule synthesis and involved activation of an endonuclease which was inhibited by Zn2+. The effect of 2-chlorodeoxyadenosine was prevented by addition of dipyridamole, a strong nucleoside transport inhibitor, or of deoxycytidine, previously shown to compete for uptake by deoxycytidine kinase. 2-Chlorodeoxyadenosine-induced apoptosis did not involve increases in the cytosolic Ca2+ concentration, but required the presence of intracellular Ca2+. It was not inhibited by activators of protein kinase C previously shown to inhibit Ca(2+)-dependent cell death. Addition of 2-chlorodeoxyadenosine induced an increase in the amount of p53 in human thymocytes, while 2-chloroadenosine had no effect. These data suggest that 2-chloroadenosine and 2-chlorodeoxyadenosine induce cell death in human thymocytes via different signalling pathways.
2-氯腺苷主要通过依赖钙离子的机制诱导人胸腺细胞的DNA片段化和细胞死亡。用2-氯脱氧腺苷（5 - 1000 nM）孵育人胸腺细胞也会诱导细胞死亡（凋亡），这依赖于大分子合成，并涉及一种被锌离子抑制的核酸内切酶的激活。加入双嘧达莫（一种强力核苷转运抑制剂）或脱氧胞苷（先前已证明其可竞争脱氧胞苷激酶的摄取）可阻止2-氯脱氧腺苷的作用。2-氯脱氧腺苷诱导的凋亡并不涉及胞质钙离子浓度的升高，但需要细胞内钙离子的存在。它不受先前已证明可抑制依赖钙离子的细胞死亡的蛋白激酶C激活剂的抑制。加入2-氯脱氧腺苷会导致人胸腺细胞中p53含量增加，而2-氯腺苷则没有此作用。这些数据表明，2-氯腺苷和2-氯脱氧腺苷通过不同的信号通路诱导人胸腺细胞死亡。
