| The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines. | |
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MedLine Citation:
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PMID: 21903261 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiaoling Gao; Lei Yao; Qiangxiang Song; Liang Zhu; Zheng Xia; Huimin Xia; Xinguo Jiang; Jun Chen; Hongzhuan Chen |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-6 |
Journal Detail:
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Title: Biomaterials Volume: - ISSN: 1878-5905 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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