TY - GEN
T1 - Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells
AU - Chiu, Hui Wen
AU - Xia, Tian
AU - Tsai, Jui Chen
AU - Chen, Chun Wan
AU - Wang, Ying Jan
PY - 2013
Y1 - 2013
N2 - 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. We applied bafilomycin Al, an inhibitor of autophagosome-lysosome fusion, and 3-MA, an initiator of autophagy, to determine whether inhibition of autophagy alters NH2-PS treatment-induced cytotoxicity. The results indicated a decreased autophagy flux by bafilomycin Aland an increased cell viability by 3-MA which confirm the autophagic cell death treated with NH2-PS. In addition, ER stress and signaling pathways related to the process of autophagy induced by NH2-PS in RAW 264.7 and BEAS-2B cells were examined. We found that NH2-PS significantly increased the staining of ER-specific dye and IRE la protein expression. Meanwhile, the phosphorylation of Akt/mTOR decreased and the phosphorylation of AMPK increased. Taken together, our results indicate 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.
AB - 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. We applied bafilomycin Al, an inhibitor of autophagosome-lysosome fusion, and 3-MA, an initiator of autophagy, to determine whether inhibition of autophagy alters NH2-PS treatment-induced cytotoxicity. The results indicated a decreased autophagy flux by bafilomycin Aland an increased cell viability by 3-MA which confirm the autophagic cell death treated with NH2-PS. In addition, ER stress and signaling pathways related to the process of autophagy induced by NH2-PS in RAW 264.7 and BEAS-2B cells were examined. We found that NH2-PS significantly increased the staining of ER-specific dye and IRE la protein expression. Meanwhile, the phosphorylation of Akt/mTOR decreased and the phosphorylation of AMPK increased. Taken together, our results indicate 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.
KW - Autophagy
KW - Cationic polystyrene nanosphere
KW - Endoplasmic reticulum stress
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M3 - Conference contribution
AN - SCOPUS:84881091392
SN - 9781482205862
T3 - Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013
SP - 385
EP - 387
BT - Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013
T2 - Nanotechnology 2013: Bio Sensors, Instruments, Medical, Environment and Energy - 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013
Y2 - 12 May 2013 through 16 May 2013
ER -
