Early growth response-1 contributes to steatosis development after acute ethanol administration.
Early growth response-1 contributes to steatosis development after acute ethanol administration.
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DOI：
10.1111/j.1530-0277.2011.01681.x
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Davis JS
中科院分区：
文献类型：
--
作者：
Donohue TM Jr;Osna NA;Trambly CS;Whitaker NP;Thomes PG;Todero SL;Davis JS
先前的工作表明，转录因子，早期生长反应-1（Egr-1）参与慢性乙醇给药后脂肪变性（脂肪肝）的发展。在这里，我们确定了Egr-1参与急性乙醇给药小鼠脂肪肝发展的程度。在急性研究中，我们通过胃插管用乙醇或磷酸盐缓冲盐水（PBS）处理野生型和Egr-1缺失小鼠。在治疗后的不同时间，我们收获血清和肝脏，定量内毒素，肝损伤指数，脂肪变性和肝脏Egr-1含量。在慢性研究中，给各组小鼠喂食含有乙醇或等热量麦芽糖糊精的流质饮食7-8周。与对照组相比，急性乙醇处理的小鼠在处理后30分钟开始出现血清内毒素的快速、短暂升高。灌胃后1小时，乙醇处理小鼠的肝脏表现出Egr-1 mRNA和蛋白质的强烈升高。灌胃后3小时，乙醇处理小鼠的肝脏甘油三酯增加，脂质过氧化反应也增加。急性乙醇治疗Egr-1-null小鼠没有表现出Egr-1的表达，但这些动物仍然发展甘油三酯升高，虽然显着低于乙醇喂养的野生型同窝出生。尽管显示脂肪肝减少，乙醇处理的Egr-1基因敲除小鼠表现出更大的肝损伤。慢性乙醇喂养后，脂肪变性和肝脏肿大明显，但没有内毒素升高的迹象。乙醇喂养的小鼠中的Egr-1水平与成对喂养的对照组相同。急性乙醇给药诱导小鼠肝脏中Egr-1的合成。然而，尽管其强劲的增长，转录因子有一个较小的，但显着的，在脂肪变性发展后，急性乙醇处理的功能。我们认为，急性乙醇后Egr-1的升高是对由乙醇代谢和内毒素水平升高引发的酗酒引起的急性肝损伤的一种保肝适应。
Previous work demonstrated that the transcription factor, early growth response-1 (Egr-1) participates in the development of steatosis (fatty liver) after chronic ethanol administration. Here, we determined the extent to which Egr-1 is involved in fatty liver development in mice subjected to acute ethanol administration. In acute studies, we treated both wild type and Egr-1 null mice with either ethanol or phosphate-buffered saline (PBS) by gastric intubation. At various times after treatment, we harvested sera and livers and quantified endotoxin, indices of liver injury, steatosis, and hepatic Egr-1 content. In chronic studies, groups of mice were fed liquid diets containing either ethanol or isocaloric maltose-dextrin for 7-8 weeks. Compared with controls, acute ethanol-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30 minutes after treatment. One hour post-gavage, livers from ethanol-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By three hours post-gavage, liver triglyceride increased in ethanol-treated mice as did lipid peroxidation. Acute ethanol treatment of Egr-1-null mice showed no Egr-1 expression, but these animals still developed elevated triglycerides, although significantly lower than ethanol-fed wild-type littermates. Despite showing decreased fatty liver, ethanol-treated Egr-1 null mice exhibited greater liver injury. After chronic ethanol feeding, steatosis and liver enlargement were clearly evident, but there was no indication of elevated endotoxin. Egr-1 levels in ethanol-fed mice were equal to those of pair-fed controls. Acute ethanol administration induced the synthesis of Egr-1 in mouse liver. However, despite its robust increase, the transcription factor had a smaller, albeit significant, function in steatosis development after acute ethanol treatment. We propose that the rise in Egr-1 after acute ethanol is an hepatoprotective adaptation to acute liver injury from binge drinking that is triggered by ethanol metabolism and elevated levels of endotoxin.
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