Cationic polystyrene nanosphere induces autophagy through inhibition of Akt/mTOR and activation of AMPK signaling pathways in macrophage and epithelial cells

H-W Chiu, T. Xia, J-C Tsai, C-W Chen, Y-J Wang
National Cheng Kung University, Medical College, TW

Keywords: cationic polystyrene nanosphere, autophagy, endoplasmic reticulum stress


Nanoparticles have been used to produce a wide range of products. Those include applications in imaging and drug delivery in medicine. However, the possible adverse biological effects in human being remain unclear. Autophagy is an important catabolic process responsible for degrading and recycling long-lived proteins, cellular aggregates and damaged organelles. In addition to the well-documented role of autophagy in cell survival, a function for autophagy in cell death has long been proposed. Polystyrene could be used as biosensor and drug delivery carrier. It has been reported that cationic polystyrene (NH2-PS) could induce cell death in RAW 264.7 and BEAS-2B cells through apoptotic and necrotic cell death. Our current study further demonstrated that autophagic cell death could also be induced by NH2-PS. In addition, we found that NH2-PS significantly increased the staining of ER-specific dye and IRE1α protein expression. Meanwhile, the phosphorylation of Akt/mTOR decreased and the phosphorylation of AMPK increased. Thus, we conclude that NH2-PS-induced autophagic cell death was mainly occurred through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways. Specifically, NH2-PS induced ER stress in RAW and BEAS-2B cells. Thus, autophagy can be considered as an additional mechanism providing intracellular selectivity for introduced NH2-PS nanospheres.