Ethanol-regulated genes that contribute to ethanol sensitivity and rapid tolerance in Drosophila.
Ethanol-regulated genes that contribute to ethanol sensitivity and rapid tolerance in Drosophila.
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DOI：
10.1111/j.1530-0277.2009.01093.x
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Wolf FW
中科院分区：
文献类型：
--
作者：
Kong EC;Allouche L;Chapot PA;Vranizan K;Moore MS;Heberlein U;Wolf FW
酒精摄入量的增加是酒精使用障碍发展的一个主要预测因素，对药物的有害和令人愉快的影响的耐受性的发展促进了这一点。乙醇耐受性形成的分子机制是复杂的，目前还不清楚。为了确定导致酒精耐受性的遗传机制，我们研究了单次镇静剂量的乙醇引起果蝇基因表达变化的时间进程，并完成了对存在乙醇调节基因突变的菌株的行为调查。新陈代谢、核酸结合、嗅觉、信号转导调节和应激等基因的丰富表明，这些生物过程受到酒精暴露的协同影响。我们还检测到Toll和IMD先天免疫信号转导通路中基因的协同上调。一项多项研究的比较显示，有一小部分基因显示出类似的调节，包括丝氨酸生物合成的3个基因表达增加。一项含有乙醇调节基因突变的果蝇品系的调查显示，乙醇对乙醇的敏感性和耐受性表型在丝氨酸生物合成、嗅觉、转录调节、免疫和新陈代谢中起作用。嗅觉共受体Or83b或sirtuin Sir2编码基因缺失的果蝇在酒精耐受性的发展中显示出显著的变化。我们的发现暗示了这些基因在调节酒精行为反应中的新作用。
Increased ethanol intake, a major predictor for the development of alcohol use disorders, is facilitated by the development of tolerance to both the aversive and pleasurable effects of the drug. The molecular mechanisms underlying ethanol tolerance development are complex and are not yet well understood. To identify genetic mechanisms that contribute to ethanol tolerance, we examined the time course of gene expression changes elicited by a single sedating dose of ethanol in Drosophila, and completed a behavioral survey of strains harboring mutations in ethanol-regulated genes. Enrichment for genes in metabolism, nucleic acid binding, olfaction, regulation of signal transduction, and stress suggests that these biological processes are coordinately affected by ethanol exposure. We also detected a coordinate up-regulation of genes in the Toll and Imd innate immunity signal transduction pathways. A multi-study comparison revealed a small set of genes showing similar regulation, including increased expression of 3 genes for serine biosynthesis. A survey of Drosophila strains harboring mutations in ethanol-regulated genes for ethanol sensitivity and tolerance phenotypes revealed roles for serine biosynthesis, olfaction, transcriptional regulation, immunity, and metabolism. Flies harboring deletions of the genes encoding the olfactory co-receptor Or83b or the sirtuin Sir2 showed marked changes in the development of ethanol tolerance. Our findings implicate novel roles for these genes in regulating ethanol behavioral responses.
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影响因子：
9.8
作者：
Benton, Richard;Sachse, Silke;Michnick, Stephen W;Vosshall, Leslie B
通讯作者：
Vosshall, Leslie B
DOI：
10.1097/01.alc.0000141817.15993.98
发表时间：
2004-10-01
影响因子：
3.2
作者：
Berger, KH;Heberlein, U;Moore, MS
通讯作者：
Moore, MS
影响因子：
11.8
作者：
De Gregorio, E;Han, SJ;Brey, PT
通讯作者：
Brey, PT
影响因子：
56.9
作者：
LOVINGER, DM;WHITE, G;WEIGHT, FF
通讯作者：
WEIGHT, FF
DOI：
10.1097/01.alc.0000122764.60626.af
发表时间：
2004-04-01
影响因子：
3.2
作者：
Kareken, DA;Claus, ED;Li, TK
通讯作者：
Li, TK