摘要
当DNA损伤发生时,细胞停止细胞循环,进行DNA 修复。然而,当DNA损伤超过DNA修复能力,细胞将凋亡或者衰老。这些机制会阻止细胞用严重损坏的DNA进行增殖,从而保护器官免受癌症发展的伤害。当个体遭受压力时,下丘脑-垂体-肾上腺(HPA)轴和交感-肾上腺-骨髓质(SAM)系统可能会被激活,分别造成糖皮质激素和儿茶酚胺的分泌。这些压力相关荷尔蒙的影响被推荐用来促进细胞衰老。但是与此矛盾的是,HPA轴的长期兴奋与更高风险癌症发生率有关。关于DNA损伤反应途径,这篇综述讨论了究竟压力荷尔蒙会诱发衰老还是肿瘤发展或者是两者都是,历史和现在的数据会帮助我们解决这些争论。
关键词: 儿茶酚胺,DNA损伤反应,糖皮质激素,细胞衰老,肿瘤进展。
图形摘要
Current Drug Targets
Title:Stress Hormone-Mediated DNA Damage Response -- Implications for Cellular Senescence and Tumour Progression
Volume: 17 Issue: 4
Author(s): Maria Moreno-Villanueva and Alexander Burkle
Affiliation:
关键词: 儿茶酚胺,DNA损伤反应,糖皮质激素,细胞衰老,肿瘤进展。
摘要: When DNA damage occurs, cells stop the cell cycle and DNA repair can take place. However, if DNA damage exceeds DNA repair capacities, cells undergo either apoptosis or senescence. These mechanisms preclude the proliferation of cells with heavily damaged DNA, thus protecting the organism against tumour development.
When individuals are exposed to stress, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic- adrenal-medullary (SAM) system can be activated leading to secretion of corticosteroids and catecholamines, respectively. The influences of these stress-related hormones have been proposed to promote cellular senescence. But paradoxically, chronic stimulation of the HPA axis is associated with higher risk of developing cancer.
Focusing on the DNA damage response pathway, this review discusses whether stress hormones induce senescence or tumour progression or both and presents historical and recent data that might help resolve some of these controversies.
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Maria Moreno-Villanueva and Alexander Burkle , Stress Hormone-Mediated DNA Damage Response -- Implications for Cellular Senescence and Tumour Progression, Current Drug Targets 2016; 17 (4) . https://dx.doi.org/10.2174/1389450116666151001113720
DOI https://dx.doi.org/10.2174/1389450116666151001113720 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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