昼夜节律基因在果蝇对乙醇的耐受性上存在差异影响。
Circadian genes differentially affect tolerance to ethanol in Drosophila.
机构信息
The Waggoner Center for Alcohol and Addiction Research , Section of Neurobiology, The University of Texas at Austin, Austin, Texas.
出版信息
Alcohol Clin Exp Res. 2013 Nov;37(11):1862-71. doi: 10.1111/acer.12173. Epub 2013 Jun 28.
BACKGROUND
There is a strong relationship between circadian rhythms and ethanol (EtOH) responses. EtOH consumption has been shown to disrupt physiological and behavioral circadian rhythms in mammals (Alcohol Clin Exp Res 2005b, 29, 1550). The Drosophila central circadian pacemaker is composed of proteins encoded by the per, tim, cyc, and Clk genes. Using Drosophila mutant analysis, we asked whether these central components of the circadian clock make the equivalent contribution toward EtOH tolerance and whether rhythmicity itself is necessary for tolerance.
METHODS
We tested flies carrying mutations in core clock genes for the capacity to acquire EtOH tolerance. Tolerance was assayed by comparing the sedation curves of populations during their first and second sedation. Animals that had acquired tolerance sedated more slowly. Movement was also monitored as the flies breathe the EtOH vapor to determine if other facets of the EtOH response were affected by the mutations. Gas chromatography was used to measure internal EtOH concentration. Constant light was used to nongenetically destabilize the PER and TIM proteins.
RESULTS
A group of circadian mutations, all of which eliminate circadian rhythms, do not disrupt tolerance identically. Mutations in per, tim, and cyc completely block tolerance. However, a mutation in Clk does not interfere with tolerance. Constant light also disrupts the capacity to acquire tolerance. These lines did not differ in EtOH absorption.
CONCLUSIONS
Mutations affecting different parts of the intracellular circadian clock can block the capacity to acquire rapid EtOH tolerance. However, the role of circadian genes in EtOH tolerance is independent of their role in producing circadian rhythmicity. The interference in the capacity to acquire EtOH tolerance by some circadian mutations is not merely a downstream effect of a nonfunctional circadian clock; instead, these circadian genes play an independent role in EtOH tolerance.
背景
昼夜节律与乙醇（EtOH）反应之间存在很强的关系。已经表明，乙醇的消耗会破坏哺乳动物的生理和行为昼夜节律（Alcohol Clin Exp Res 2005b，29，1550）。果蝇的中央生物钟由 per、tim、cyc 和 Clk 基因编码的蛋白质组成。通过使用果蝇突变分析，我们询问这些生物钟的核心组成部分是否对乙醇耐受性做出等效贡献，以及节律性本身是否对耐受性是必需的。
方法
我们测试了携带核心时钟基因突变的果蝇获得乙醇耐受性的能力。通过比较种群在第一次和第二次镇静期间的镇静曲线来检测耐受性。获得耐受性的动物镇静得更慢。还监测了动物的运动，因为它们呼吸乙醇蒸气，以确定乙醇反应的其他方面是否受到突变的影响。气相色谱法用于测量内部乙醇浓度。恒定光照用于非遗传地破坏 PER 和 TIM 蛋白的稳定性。
结果
一组昼夜节律突变，都消除了昼夜节律，不会以相同的方式破坏耐受性。per、tim 和 cyc 的突变完全阻断了耐受性。然而，Clk 的突变不干扰耐受性。恒定光照也破坏了获得耐受性的能力。这些品系在乙醇吸收方面没有差异。
结论
影响细胞内生物钟不同部分的突变可以阻断快速获得乙醇耐受性的能力。然而，昼夜节律基因在乙醇耐受性中的作用与其产生昼夜节律性的作用是独立的。一些昼夜节律突变干扰获得乙醇耐受性的能力不仅仅是功能失调的生物钟的下游效应；相反，这些昼夜节律基因在乙醇耐受性中发挥独立作用。
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