Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells.
Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells.
复制标题
长期服用乙醇会改变肝内皮细胞对乙醛加合物的降解。
DOI：
10.1002/hep.510240329
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Tuma,DJ
中科院分区：
文献类型：
--
作者：
Thiele,GM;Miller,JA;Klassen,LW;Tuma,DJ
先前的报道表明，长期给药乙醇会改变肝内皮细胞（LEC）对多种大分子的受体介导的内吞作用（RME）。乙醛是乙醇代谢的主要代谢产物，已被证明与蛋白质结合形成加合物。在这项研究中，研究了乙醛修饰蛋白在LEC吸收和降解乙醛修饰蛋白所必需的蛋白质修饰水平。牛血清白蛋白（BSA）乙醛加合物是通过白蛋白与乙醛在100 mmol/L条件下在37℃孵育1小时，在1 mmol/L或0.2 mmol/L条件下在37℃孵育5天制备的。这些加合物的存在导致在4小时内分别降解107+/ -10.02 μ g、69.82+/ -5 μ g和2.5+/ -0.42 μ g的乙醛加合物。在乙醇喂养的大鼠肝脏中，这些值分别下降了53%、67%和近100%。此外，用1 mmol/L的乙醛在不同的时间和/或pH下修饰蛋白质，改变了14c -乙醛结合的数量，但没有观察到降解的显著变化。最后，过量的甲醛修饰白蛋白完全抑制了乙醛加合物的降解，表明它们使用相同的受体。这些数据表明乙醛修饰的蛋白质可能被LEC上的清道夫受体吸收和降解。这种吸收和降解取决于乙醛对蛋白质的修饰程度，长期的乙醇消耗会降低乙醛-蛋白质加合物的降解。
Previous reports have shown that long–term ethanol administration alters receptor–mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde–modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37 degrees C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37 degrees C. In situliver perfusion in the presence of these adducts resulted in the degradation of 107+/–10.02 microg, 69.82+/–5 microg, and 2.5+/–0.42 microg of acetaldehyde–adducted albumin, respectively, during a 4–hour period. These values were decreased by 53%, 67%, and nearly 100%, respectively, in livers from ethanol–fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14 C–acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde–modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde–modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long–term ethanol consumption decreases the degradation of acetaldehyde–protein adducts.