Wang S L, Feng J, Wu-Wang C Y
Dental Research Center, UMDNJ-NJ Dental School, University Heights, Newark 07103-2400, USA.
Toxicol Lett. 1997 Feb 7;90(2-3):115-23. doi: 10.1016/s0378-4274(96)03836-2.
This study investigated the time-dependent effects of ethanol (EtOH) feeding on epidermal growth factor binding and epidermal growth factor-mediated functions in the stomach. Adult male rats were fed either an isocaloric control or EtOH-containing liquid diet (36% total calories as EtOH) for 2, 4 and 6 weeks. At the end of each feeding period, animals were sacrificed and the stomach was dissected for the sample preparation. EtOH caused a time-dependent alteration (r = 0.89) of the 125I-epidermal growth factor binding to the gastric mucosal membrane (% control: week 2, 114%; week 4, 64%* and week 6, 45%*, n = 5, *P < 0.05). Protein kinase analysis also showed that EtOH caused a time-dependent decrease of epidermal growth factor-stimulated autophosphorylation of epidermal growth factor receptor protein (180 kDa) during three feeding periods. Western blot analysis, using anti-tyrosine phosphorylated epidermal growth factor receptor (active form) antibody, revealed a major immunoreactive protein band (180 kDa) in all samples pre-incubated with 1 microM epidermal growth factor. Consistent with data from kinase analysis, treatment of EtOH decreased the immunoreactivity of the active form of epidermal growth factor receptor (180 kDa) in the stomach. In conclusion, EtOH feeding caused a time-dependent alteration of epidermal growth factor receptor in the stomach, which may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.
本研究调查了乙醇（EtOH）喂养对胃中表皮生长因子结合及表皮生长因子介导功能的时间依赖性影响。成年雄性大鼠分别给予等热量对照饮食或含乙醇的液体饮食（乙醇提供总热量的36%），持续2、4和6周。在每个喂养期结束时，处死动物并解剖胃部以进行样本制备。乙醇导致125I-表皮生长因子与胃黏膜膜结合出现时间依赖性改变（r = 0.89）（对照百分比：第2周，114%；第4周，64%；第6周，45%，n = 5，*P < 0.05）。蛋白激酶分析还显示，在三个喂养期内，乙醇导致表皮生长因子刺激的表皮生长因子受体蛋白（180 kDa）自磷酸化出现时间依赖性下降。使用抗酪氨酸磷酸化表皮生长因子受体（活性形式）抗体进行的蛋白质印迹分析显示，在所有预先与1 microM表皮生长因子孵育的样本中，有一条主要的免疫反应性蛋白带（180 kDa）。与激酶分析数据一致，乙醇处理降低了胃中表皮生长因子受体活性形式（180 kDa）的免疫反应性。总之，乙醇喂养导致胃中表皮生长因子受体出现时间依赖性改变，这可能是与酒精滥用相关的胃部病理的潜在机制之一。
