Geer B W, Dybas L K, Shanner L J
Department of Biology, Knox College, Galesburg, Illinois 61401.
J Exp Zool. 1989 Apr;250(1):22-39. doi: 10.1002/jez.1402500105.
Exposure of early third instar larvae of Drosophila melanogaster to a nonlethal dose of ethanol was detrimental to larvae lacking alcohol dehydrogenase (ADH) but beneficial to wild-type larvae in terms of surviving a later ethanol tolerance test, indicating that one of the important functions of the ADH system is to supply derivatives of ethanol to larvae that in turn promote ethanol tolerance. High intracellular concentrations of ethanol in ADH-deficient (Adhn2) larvae fed ethanol were accompanied by a decrease in the cell membrane infoldings of fat body cells, suggesting that the capacities to absorb and release molecules were reduced. Marked effects of ethanol on the endoplasmic reticulum and mitochondria of ADH-deficient larvae were also evident. The absence of similar changes in wild-type larvae that were fed moderate levels of ethanol showed that the ADH system kept the intracellular level of ethanol at a concentration low enough to avoid cell damage. A cytometric analysis of electron micrographs showed that there were ethanol-induced reductions in glycogen, lipid, and protein stores in the fat body cells of ADH-deficient larvae fed 1.25% ethanol (v/v) compared with null larvae fed an ethanol-free diet. This finding implied that the capacities to synthesize or store these compounds may be limited by high intracellular concentrations of ethanol. The cytometric analysis also revealed that the consumption of diets containing 2.5% and 4.5% ethanol by Canton-S wild-type larvae for 3 days after 4 days of feeding on an ethanol-free diet resulted in decreases in glycogen and protein deposits in fat body cells, but increased the amount of lipid deposits compared to larvae fed an ethanol-free diet. This observation, coupled with the greater weight of wild-type adults that were fed a growth-limiting concentration of ethanol compared with control adults, suggested that a metabolic defense mechanism in larvae is to convert toxic ethanol to nontoxic storage products. Dietary ethanol alone and in combination with isopropanol stimulated an increase in the size of the NAD-pool in larvae, a condition that may favor the activity of ADH. A low dietary level of isopropanol (1%) completely blocked glycogen deposition in wild-type larvae, whereas ethanol did not. Thus ethanol and isopropanol exert some different toxic effects on larval fat bodies.
将黑腹果蝇早期三龄幼虫暴露于非致死剂量的乙醇中，对缺乏乙醇脱氢酶（ADH）的幼虫有害，但对野生型幼虫而言，在随后的乙醇耐受性测试中存活下来却有益，这表明ADH系统的重要功能之一是为幼虫提供乙醇衍生物，进而促进乙醇耐受性。给缺乏ADH（Adhn2）的幼虫喂食乙醇后，其细胞内乙醇浓度较高，同时脂肪体细胞的细胞膜褶皱减少，这表明吸收和释放分子的能力降低。乙醇对缺乏ADH的幼虫的内质网和线粒体也有明显影响。给野生型幼虫喂食适量乙醇后未出现类似变化，这表明ADH系统将细胞内乙醇水平维持在足够低的浓度，以避免细胞损伤。对电子显微镜照片的细胞计量分析表明，与喂食无乙醇饮食的对照幼虫相比，给喂食1.25%乙醇（v/v）的缺乏ADH的幼虫的脂肪体细胞中，乙醇会导致糖原、脂质和蛋白质储存减少。这一发现意味着合成或储存这些化合物的能力可能受到细胞内高浓度乙醇的限制。细胞计量分析还显示，在无乙醇饮食喂养4天后，Canton-S野生型幼虫食用含2.5%和4.5%乙醇的饮食3天，导致脂肪体细胞中的糖原和蛋白质沉积减少，但与喂食无乙醇饮食的幼虫相比，脂质沉积量增加。这一观察结果，再加上喂食生长限制浓度乙醇的野生型成虫比对照成虫体重更重，表明幼虫的一种代谢防御机制是将有毒乙醇转化为无毒储存产物。单独的饮食乙醇以及与异丙醇联合使用会刺激幼虫体内NAD池大小增加，这种情况可能有利于ADH的活性。低饮食水平的异丙醇（1%）完全阻断了野生型幼虫中的糖原沉积，而乙醇则没有。因此，乙醇和异丙醇对幼虫脂肪体产生了一些不同的毒性作用。
