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The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines

Paper ID Volume ID Publish Year Pages File Format Full-Text
7253 542 2011 13 PDF Available
Title
The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines
Abstract

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.

Keywords
Biocompatibility; Polyethylenimine; Autophagy; Necrosis; Apoptosis; Cytotoxicity
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The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 33, November 2011, Pages 8613–8625
Authors
, , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us