پديدآورندگان :
Afkhami-Goli Amir a-afkhami@um.ac.ir Devision of Pharmacology, Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran , Dabbaghi Maryam Devision of Pharmacology, Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran , Kazemi Oskuee Reza Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.and Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran , Hashemi Khadijeh Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
كليدواژه :
Cytotoxicity , ER , stress , PEI , UPR
چكيده فارسي :
Among all kinds of gene delivery systems which are used for gene therapy, the cationic polymer polyethyleneimine (PEI) is used as non-viral gene delivery vector. But there are still concerns about its mechanism and magnitude of cytotoxicity. While any cell insult can led to unfolded/misfolded protein accumulation and its consequent response pathways, unfold protein response (UPR), evaluating the expression profile of ER-stress genes would be a sensitive indicator of cell stress. By transfecting Neurons, besides cytotoxicity assays, we used real-time RT-PCR to investigate the effects of PEI nanoparticles and PEI delivering plasmid (in different PEI/Plasmid ratios) on the endoplasmic reticulum, as a central contributor organelle in protein synthesis. Evaluation of the transcript levels of main central markers of ER stress (Grp78 (Bip), Atf4 and Chop, and splicing of Xbp1) shows that treating Neurons by PEI and PEI (with plasmid containing GFP reporter) can induce cell toxicity in a concentration-dependent manner. Besides that, using the lowest possible ratios of PEI/plasmid would minimize the adverse effects of PEI on cells and confers it a beneficial therapeutic importance in delivering nucleic acid based treatments.
