Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity.
Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity.
复制标题
DOI：
10.1186/gb-2007-8-6-r122
复制
发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Freedman, Jonathan H.
中科院分区：
文献类型：
--
作者：
Cui, Yuxia;McBride, Sandra J.;Boyd, Windy A.;Alper, Scott;Freedman, Jonathan H.
对秀丽隐杆线虫镉暴露的转录反应的整体分析揭示了参与细胞运输、代谢过程和蛋白水解的基因以及信号蛋白 KEL-8 的作用。接触镉与多种人类疾病有关。在低浓度下，镉会激活应激反应基因的转录，从而可以预防或修复这种金属造成的不利影响。使用秀丽隐杆线虫，鉴定出 290 个基因在暴露于镉 4 或 24 小时后出现差异表达（>1.5 倍）。其中一些基因已知参与金属解毒，包括 mtl-1、mtl-2、cdr-1 和 ttm-1，证实了该研究的功效。然而，大多数以前与金属响应性无关并且是新颖的。基因本体分析将这些基因映射到细胞/离子运输、代谢酶和蛋白水解类别。 RNA 干扰介导的 50 个镉响应基因的抑制导致对镉毒性的敏感性增加，表明这些基因参与了对镉毒性的抵抗。通过相互作用组分析鉴定了几种功能性蛋白质相互作用网络。在一个网络中，信号蛋白 KEL-8 被鉴定出来。 Kel-8 以 mek-1 (MAPKK) 依赖性方式保护线虫免受镉毒性。由于许多线虫基因和信号转导途径在进化上是保守的，因此这些结果可能有助于理解各种基因在高等生物体镉毒性中的功能作用。
Global analysis of the transcriptional response to cadmium exposure in Caenorhabditis elegans reveals roles for genes involved in cellular trafficking, metabolic processes and proteolysis, and for the signaling protein KEL-8. Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. Using Caenorhabditis elegans, 290 genes were identified that are differentially expressed (>1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms.
登录
查看更多内容
DOI：
10.1073/pnas.141004698
发表时间：
2001-07-17
影响因子：
11.1
作者：
Hanazawa, M;Mochii, M;Iino, Y
通讯作者：
Iino, Y
DOI：
10.1016/s1532-0456(01)00165-x
发表时间：
2001-03-01
影响因子：
3.9
作者：
Hermesz, E;Abrahám, M;Nemcsók, J
通讯作者：
Nemcsók, J
影响因子：
6.1
作者：
HOLT, D;WEBB, M
通讯作者：
WEBB, M
影响因子：
1.6
作者：
Boroskova, Z;Dvoroznakova, E
通讯作者：
Dvoroznakova, E
影响因子：
4.5
作者：
DE, SK;DEY, SK;ANDREWS, GK
通讯作者：
ANDREWS, GK