Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin-dependent kinases
Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin-dependent kinases
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DOI：
10.1016/j.molimm.2006.02.013
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Freed, Brian M.
中科院分区：
文献类型：
--
作者：
Frazer-Abel, Ashley A.;McCue, Jesica M.;Freed, Brian M.
吸烟导致肺部T细胞反应的严重抑制，这与呼吸道感染的易感性增加和肿瘤监测减少有关。我们以前证明，香烟焦油中的酚类化合物抑制胚细胞发生，干扰人类T细胞周期进程。为了确定细胞周期阻滞发生的机制，我们研究了这些化合物对控制G（0）/G（1）转换的细胞周期蛋白依赖性激酶（Cdk）的影响。我们发现，对苯二酚抑制Cdk 4和Cdk 6激酶活性的诱导> 80%，而邻苯二酚和苯酚的抑制作用明显较弱。HQ不影响Cdk 6蛋白的促有丝分裂诱导，但抑制细胞周期蛋白D3的表达> 90%，导致适当的Cdk 6/细胞周期蛋白D3复合物形成的显著减少。(c)2006爱思唯尔有限公司保留所有权利。
Cigarette smoking causes profound suppression of pulmonary T cell responses, which is associated with increased susceptibility to respiratory tract infections and decreased tumor surveillance. We previously demonstrated that the phenolic compounds in cigarette tar inhibit blastogenesis and interfere with human T cell cycle progression. To identify the mechanism by which cell cycle arrest occurs, we examined the effects of these compounds on cyclin-dependent kinases (Cdk) that control the G(0)/G(1) transition. We found that hydroquinone inhibited induction of Cdk4 and Cdk6 kinase activities by > 80%, while catechol and phenol were markedly less potent. HQ did not affect mitogenic induction of the Cdk6 protein, but inhibited expression of cyclin D3 by > 90% resulting in a dramatic reduction in proper Cdk6/Cyclin D3 complex formation. (c) 2006 Elsevier Ltd. All rights reserved.