Ethanol tolerance caused by slowpoke induction in drosophila
Ethanol tolerance caused by slowpoke induction in drosophila
复制标题
DOI：
10.1111/j.1530-0277.2006.00087.x
复制
发表时间：
2006-05-01
影响因子：
3.2
通讯作者：
Atkinson, NS
中科院分区：
文献类型：
--
作者：
Cowmeadow, RB;Krishnan, HR;Atkinson, NS
背景资料：最近，由慢波基因编码的大电导钙激活钾通道与乙醇反应有关。携带该基因突变的秀丽隐杆线虫改变了对乙醇的敏感性，而该基因的果蝇突变体不能获得对乙醇或麻醉剂的快速耐受性。在果蝇中，慢波表达的诱导已被链接到麻醉resistance.Methods：我们使用果蝇作为一个模型系统来检查慢波表达和乙醇耐受性之间的关系。实时PCR和报告基因用于测量乙醇镇静后的慢波诱导。一个诱导型的slowpoke转基因被用来操纵slowpoke水平在没有乙醇sediment.Results：乙醇镇静增加转录从slowpoke神经启动子，但不是从slowpoke肌肉/气管细胞启动子。这种神经特异性变化伴随着乙醇耐受的出现，使我们怀疑两者之间的联系。此外，从转基因的诱导慢波表达产生的表型，模仿乙醇tolerance.Conclusions：在果蝇，乙醇镇静诱导慢波在神经系统中的表达和乙醇耐受性的结果。单独诱导慢波表达足以产生与真正的乙醇耐受性无法区分的表型。因此，慢波BK型通道基因的调节必须在果蝇乙醇反应中发挥不可或缺的作用。
Background: The large-conductance calcium-activated potassium channel encoded by the slowpoke gene has recently been implicated in the ethanol response. Caenorhabditis elegans carrying mutations in this gene have altered ethanol sensitivity and Drosophila mutant for this gene are unable to acquire rapid tolerance to ethanol or anesthetics. In Drosophila, induction of slowpoke expression has been linked to anesthetic resistance.Methods: We used Drosophila as a model system to examine the relationship between slowpoke expression and ethanol tolerance. Real-time PCR and a reporter transgene were used to measure slowpoke induction after ethanol sedation. An inducible slowpoke transgene was used to manipulate slowpoke levels in the absence of ethanol sedation.Results: Ethanol sedation increased transcription from the slowpoke neural promoters but not from the slowpoke muscle/tracheal cell promoters. This neural-specific change was concomitant with the appearance of ethanol tolerance, leading us to suspect linkage between the two. Moreover, induction of slowpoke expression from a transgene produced a phenotype that mimics ethanol tolerance.Conclusions: In Drosophila, ethanol sedation induces slowpoke expression in the nervous system and results in ethanol tolerance. The induction of slowpoke expression alone is sufficient to produce a phenotype that is indistinguishable from true ethanol tolerance. Therefore, the regulation of the slowpoke BK-type channel gene must play an integral role in the Drosophila ethanol response.