Wang Yan-Ling, Hu Richard, Lugea Aurelia, Gukovsky Ilya, Smoot Duane, Gukovskaya Anna S, Pandol Stephen J
USC-UCLA Research Center for Alcohol Liver and Pancreatic Diseases, University of California, Los Angeles, USA.
Pancreas. 2006 May;32(4):351-9. doi: 10.1097/01.mpa.0000220859.93496.e1.
Alcohol abuse is a major cause of pancreatitis, which is associated with death of parenchymal cells. The goal of this study was to explore the effects of ethanol on cell death pathways in the pancreas.
Adult male Wistar rats were fed with ethanol diets using the Lieber-DeCarli method. Caspase-8, caspase-3, and cathepsin B expression and activity in the pancreas of these animals as well as the signals that regulate their expression were studied using Western blot analysis and specific assays for biochemical enzyme activity.
In the pancreas from rats fed with ethanol, the protein expression and activity of caspase-8 decreased by 48% and 45%, respectively, and caspase-3 activity decreased by 39%. In contrast, cathepsin B protein expression and activity increased with ethanol feeding by 189% and 143%, respectively. Evaluation of the transcriptional regulatory system for caspase-8 and cathepsin B showed that the ethanol effects on these pathways were largely transcriptional.
Our findings show effects of ethanol on the expression of several signals involved in cell death in the pancreas through alteration of transcriptional regulators. The decrease in caspase expression and increase in cathepsin B expression indicate that ethanol feeding may prevent apoptosis and promote necrosis of pancreatic tissue with stresses that cause pancreatitis.
酒精滥用是胰腺炎的主要病因，胰腺炎与实质细胞死亡相关。本研究的目的是探讨乙醇对胰腺细胞死亡途径的影响。
采用Lieber-DeCarli法用乙醇饲料喂养成年雄性Wistar大鼠。使用蛋白质印迹分析和生化酶活性特异性检测方法，研究这些动物胰腺中半胱天冬酶-8、半胱天冬酶-3和组织蛋白酶B的表达及活性，以及调节它们表达的信号。
在喂食乙醇的大鼠胰腺中，半胱天冬酶-8的蛋白质表达和活性分别下降了48%和45%，半胱天冬酶-3活性下降了39%。相反，组织蛋白酶B的蛋白质表达和活性在喂食乙醇后分别增加了189%和143%。对半胱天冬酶-8和组织蛋白酶B转录调节系统的评估表明，乙醇对这些途径的影响主要是转录性的。
我们的研究结果表明，乙醇通过改变转录调节因子，对胰腺中参与细胞死亡的几种信号的表达产生影响。半胱天冬酶表达的降低和组织蛋白酶B表达的增加表明，喂食乙醇可能会在导致胰腺炎的应激状态下，阻止胰腺组织的凋亡并促进其坏死。
