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

Hui Wen Chiu, Tian Xia, Jui Chen Tsai, Chun Wan Chen, Ying Jan Wang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

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.

Original languageEnglish
Title of host publicationTechnical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013
Pages385-387
Number of pages3
Volume3
Publication statusPublished - 2013
Externally publishedYes
EventNanotechnology 2013: Bio Sensors, Instruments, Medical, Environment and Energy - 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013 - Washington, DC, United States
Duration: May 12 2013May 16 2013

Other

OtherNanotechnology 2013: Bio Sensors, Instruments, Medical, Environment and Energy - 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013
CountryUnited States
CityWashington, DC
Period5/12/135/16/13

Fingerprint

Nanospheres
AMP-Activated Protein Kinases
Polystyrenes
Autophagy
Epithelial Cells
Macrophages
Cell Death
Cell Survival
Phosphorylation
Drug Carriers
Recycling
Biosensing Techniques
Lysosomes
Organelles
Nanoparticles
Coloring Agents

Keywords

  • Autophagy
  • Cationic polystyrene nanosphere
  • Endoplasmic reticulum stress

ASJC Scopus subject areas

  • Biotechnology

Cite this

Chiu, H. W., Xia, T., Tsai, J. C., Chen, C. W., & Wang, Y. J. (2013). Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells. In Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013 (Vol. 3, pp. 385-387)

Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells. / Chiu, Hui Wen; Xia, Tian; Tsai, Jui Chen; Chen, Chun Wan; Wang, Ying Jan.

Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013. Vol. 3 2013. p. 385-387.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Chiu, HW, Xia, T, Tsai, JC, Chen, CW & Wang, YJ 2013, Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells. in Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013. vol. 3, pp. 385-387, Nanotechnology 2013: Bio Sensors, Instruments, Medical, Environment and Energy - 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013, Washington, DC, United States, 5/12/13.
Chiu HW, Xia T, Tsai JC, Chen CW, Wang YJ. Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells. In Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013. Vol. 3. 2013. p. 385-387
Chiu, Hui Wen ; Xia, Tian ; Tsai, Jui Chen ; Chen, Chun Wan ; Wang, Ying Jan. / Cationic polystyrene nanosphere induces autophagy through inhibition of the Akt/mTOR and activation of the AMPK signaling pathways in macrophage and epithelial cells. Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013. Vol. 3 2013. pp. 385-387
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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.

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