title: The association of autophagy with polyethylenimine-induced cytotoxicity 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.
authors: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, PR China.
authors: Xiaoling
authors: X
authors: Gao
authors: Lei
authors: L
authors: Yao
authors: Qiangxiang
authors: Q
authors: Song
authors: Liang
authors: L
authors: Zhu
authors: Zheng
authors: Z
authors: Xia
authors: Huimin
authors: H
authors: Xia
authors: Xinguo
authors: X
authors: Jiang
authors: Jun
authors: J
authors: Chen
authors: Hongzhuan
authors: H
authors: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002469:Cell Separation; D004285:Dogs; D004705:Endocytosis; D005434:Flow Cytometry; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D011094:Polyethyleneimine / Q000494:pharmacology*
chemical_list: D011094:Polyethyleneimine