Mechanism of telomerase induction during T cell activation
Mechanism of telomerase induction during T cell activation
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DOI：
10.1006/excr.1996.0299
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发表时间：
1996-10-10
影响因子：
3.7
通讯作者：
Chiu, CP
中科院分区：
文献类型：
--
作者：
Bodnar, AG;Kim, NW;Chiu, CP
细胞分裂过程中染色体末端（端粒）的逐渐缩短可能是复制性衰老的有丝分裂时钟。端粒酶是合成端粒DNA并维持端粒长度的核糖核蛋白，在大多数正常体细胞中不存在，但在永生细胞中表达。在外周血单个核细胞（PBMC）和造血细胞中检测到低水平的端粒酶活性，最近有报道称T细胞活化过程中端粒酶活性增加。在这项研究中，我们表明，在T细胞活化过程中端粒酶活性的增加是短暂的，并没有防止在长期的T细胞培养端粒的损失。对端粒酶诱导机制的分析表明，端粒酶活性的增加伴随着端粒酶RNA组分hTR水平的增加，而且，在阿非迪霉素存在下，端粒酶诱导也发生，表明端粒酶诱导不需要DNA合成。当用佛波酯和离子霉素激活PBMC时，观察到端粒酶表达增加，表明其不依赖于早期跨膜信号。然而，它与T细胞信号转导途径有关，因为用双吲哚马来酰亚胺抑制蛋白激酶C阻止了端粒酶活性的增加。(C)出版社：Academic Press，Inc.
The progressive shortening of the ends of chromosomes (telomeres) during cell division may serve as a mitotic clock for replicative senescence. Telomerase,a ribonucleoprotein which synthesizes telomeric DNA and maintains telomere length, is absent from most normal somatic cells but is expressed in immortal cells. Low levels of telomerase activity have been detected in peripheral blood mononuclear cells (PBMC) and hematopoietic cells and an increase in telomerase activity during T cell activation has recently been reported. In this study, we show that the increase in telomerase activity during T cell activation was transient and did not prevent the loss of telomeres in long-term T cell cultures. Analysis of the mechanism of telomerase induction showed that the increase in telomerase activity was accompanied by an increase in the levels of hTR, the RNA component of human telomerase, Moreover, telomerase induction occurred in the presence of aphidicolin, indicating that DNA synthesis was not required. Increased telomerase expression was observed when PBMC were activated with phorbol myristate acetate (PMA) and ionomycin, indicating that it was independent of early transmembrane signals. It was, however, linked to the T cell signal transduction pathway, as inhibiting protein kinase C with bisindolylmaleimide prevented the increase in telomerase activity. (C) 1996 Academic Press, Inc.