期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 377, 期 1, 页码 268-274出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.09.121
关键词
Drug-induced phospholipidosis; Cationic amphiphilic drug; Mannose 6-phosphate/IGF-II receptor; Lysosomal enzymes; Endosomes
资金
- Astellas Research Collaboration Fund
Cationic amphiphilic drugs (CADs) cause massive intracellular accumulation of phospholipids, thereby resulting in phospholipidosis (PLD); however, the molecular mechanism underlying CAD-induced PLD remains to be resolved. Here, we found that treatment of normal rat kidney cells with CADs known to induce PLD caused redistribution of a mannose 6-phosphate/IGF-II receptor (MPR300) from the TGN to endosomes and concomitantly increased the secretion of lysosomal enzymes, resulting in a decline of intracellular lysosomal enzyme levels. These results enable the interpretation of why CADs cause excessive accumulation of undegraded Substrates, including phospholipids in lysosornes, and led to the conclusion that the impaired MPR300-mediated sorting system of lysosomal enzymes reflects the general mechanism of CAD-induced PLD.. In addition, our findings Suggest that the measurement of lysosomal enzyme activity secreted into Culture medium is useful as a rapid and convenient in vitro early screening system to predict drugs that can induce PLD. (C) 2008 Elsevier Inc, All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据