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The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines.
MedLine Citation:
PMID:  21903261     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Polyethylenimine (PEI) is one of the most effective and widely used cationic macromolecules in experimental gene transfer/therapy protocols. However, the further clinical application of PEI is largely impeded by its cytotoxicity. Here we performed a fundamental investigation on the mechanism of PEI-induced cytotoxicity in both hepatic and nephritic cell lines. It was demonstrated that besides necrosis and apoptosis, autophagy was apparently associated with PEI-induced cytotoxicity and contributed to aggravated cell damage. Specifically, at the early stage (3 h) of PEI-induced cytotoxicity, autophagy was mainly correlated with lysosome damage, but in the later phase (after a 24-h recovery), autophagy was mainly related with mitochondrial injury. Modulation of Rab5, Rab7 expression and inhibition of clathrin-mediated endocytosis pathway significantly affected the formation of autophagosome, which suggested that the endolysosome transport pathway especially the clathrin-mediated endocytosis at least partly facilitated PEI-induced autophagy. As PEI-induced autophagy played a causative role in its cytotoxicity, it's highly recommended to design PEI-based gene-carriers that could avoid the endolysosome transport pathway.
Authors:
Xiaoling Gao; Lei Yao; Qiangxiang Song; Liang Zhu; Zheng Xia; Huimin Xia; Xinguo Jiang; Jun Chen; Hongzhuan Chen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-6
Journal Detail:
Title:  Biomaterials     Volume:  -     ISSN:  1878-5905     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, PR China.
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