Key Laboratory of Ion Beam Bioengineering, Chinese Academy of Sciences, Hefei, Anhui 230031, PR China.
Toxicol Mech Methods. 2009 Nov;19(9):541-6. doi: 10.3109/15376510903350363.
Many investigations showed that cobalt exposure could induce apoptosis both in cells and tissues. However, appropriate in vivo animal models to assess the underlying mechanisms of cobalt-induced apoptosis are currently unavailable. The model organism, Caenorhabditis elegans, has been shown to be a good model for evaluating many biological processes. This study detected significant cobalt induced germline cell apoptosis after 12-h exposure; thus demonstrating that C. elegans could be a mammalian in vivo substitute model to study mechanisms of apoptosis. Then knockout gene C. elegans strains were utilized to investigate the relationship between cobalt-induced apoptosis and relevant signal pathways, which were involved in DNA damage and repair, apoptosis regulation, and damage signal transduction. The results presented here demonstrated that cobalt-induced apoptosis was independent of the DNA damage response gene, such as hus-1, p53/cep-1, and egl-1. The loss-of-function of the genes that related to JNK and p38 MAPK signaling cascades suppressed cobalt-induced germline apoptosis, while ERK signaling cascades have no effect on the cobalt-induced germline apoptosis.
许多研究表明，钴暴露可诱导细胞和组织凋亡。然而，目前缺乏合适的体内动物模型来评估钴诱导凋亡的潜在机制。模式生物秀丽隐杆线虫已被证明是评估许多生物学过程的良好模型。本研究在 12 小时暴露后检测到明显的钴诱导生殖细胞凋亡；因此表明，秀丽隐杆线虫可以作为哺乳动物体内替代模型来研究凋亡机制。然后利用敲除基因的秀丽隐杆线虫品系研究钴诱导凋亡与相关信号通路之间的关系，这些信号通路涉及 DNA 损伤和修复、凋亡调控以及损伤信号转导。这里呈现的结果表明，钴诱导的凋亡不依赖于 DNA 损伤反应基因，如 hus-1、p53/cep-1 和 egl-1。与 JNK 和 p38 MAPK 信号级联相关的基因失活抑制了钴诱导的生殖细胞凋亡，而 ERK 信号级联对钴诱导的生殖细胞凋亡没有影响。
