Reduction of ethanol consumption in alcohol-preferring rats by dual expression gene transfer.
Reduction of ethanol consumption in alcohol-preferring rats by dual expression gene transfer.
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通过双表达基因转移减少嗜酒大鼠的乙醇消耗。
DOI：
10.1093/alcalc/agr161
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Tampier,Lutske
中科院分区：
文献类型：
--
作者：
Rivera-Meza,Mario;Quintanilla,MaríaElena;Tampier,Lutske
目的：在酒精中毒动物模型中，模拟携带快速乙醇脱氢酶(ADH1B*2)和失活乙醛脱氢酶(ALDH2*2)的人对酒精摄入的保护表型。方法：我们制备了携带快速大鼠ADH和针对大鼠ALDH2的反义RNA的多表达盒腺病毒载体(ADV-ADH/asALDH2)。构建了含内含子非编码DNA的腺病毒对照载体(ADV-C)。结果：注射ADV-ADH/asALDH2的大鼠肝脏ADH活性增加176%，而肝脏ALDH2活性降低24%，而给予一定剂量的乙醇(1 mg/kg，ip)后，动脉乙醛水平比注射ADV-C的动物高出400%。与对照组相比，接受AdV-ADH/asALDH2载体的大鼠的自愿酒精摄入量减少了60%。结论：本研究为通过基因转移同时增加肝脏ADH和降低ALDH活性可能构成治疗酒精中毒的一种潜在的治疗策略提供了证据。
Aims:To mimic, in an animal model of alcoholism, the protective phenotype against alcohol consumption observed in humans carrying a fast alcohol dehydrogenase (ADH1B*2) and an inactive aldehyde dehydrogenase (ALDH2*2).Methods:We developed a multiple expression cassette adenoviral vector (AdV-ADH/asALDH2) encoding both a fast rat ADH and an antisense RNA against rat ALDH2. A control adenoviral vector (AdV-C) containing intronic non-coding DNA was also developed. These adenoviral vectors were administered intravenously to rats bred as high alcohol-drinkers (University of Chile bibulous) that were previously rendered alcohol dependent by a 75-day period of voluntary 10% ethanol intake.Results:Animals administered AdV-ADH/asALDH2 showed a 176% increase in liver ADH activity, whereas liver ALDH2 activity was reduced by 24%, and upon the administration of a dose of ethanol (1 g/kg, i.p.), these showed arterial acetaldehyde levels that were 400% higher than those of animals administered AdV-C. Rats that received the AdV-ADH/asALDH2 vector reduced by 60% their voluntary ethanol intake versus controls.Conclusion:This study provides evidence that the simultaneous increase of liver ADH and a reduction of ALDH activity by gene transfer could constitute a potential therapeutic strategy for the treatment of alcoholism.
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人β1β1醇脱氢酶的结构：非活性位点取代的催化作用。
DOI：
10.1073/pnas.88.18.8149
发表时间：
1991
影响因子：
11.1
作者：
Hurley,TD;Bosron,WF;Hamilton,JA;Amzel,LM
通讯作者：
Amzel,LM
影响因子：
3.5
作者：
Kim, Dai-Jin;Choi, Ihn-Geun;Shin, Hyoung Doo
通讯作者：
Shin, Hyoung Doo
DOI：
10.1111/j.1530-0277.2008.00658.x
发表时间：
2008
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
L. Tampier;M. E. Quintanilla;Y. Israel
通讯作者：
Y. Israel
影响因子：
12.4
作者：
Reddy, PS;Sakhuja, K;Connelly, S
通讯作者：
Connelly, S
奖励和复发：酒精依赖动物模型中基因诱导的完全解离。
DOI：
10.1111/j.1530-0277.2011.01606.x
发表时间：
2012
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Quintanilla,MariaE;Tampier,Lutske;Karahanian,Eduardo;Rivera-Meza,Mario;Herrera-Marschitz,Mario;Israel,Yedy
通讯作者：
Israel,Yedy