Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy

Tsung-Lin Tsai,1,5 Chia-Cheng Hou,1,5 Hao-Chen Wang,1,5 Zih-Syuan Yang,2 Chen-Sheng Yeh,4 Dar-Bin Shieh,2,3 Wu-Chou Su1,51Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Center for Micro/Nano Science and Technology, 4Department of Chemistry, National...

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Autores principales:	Tsai TL, Hou CC, Wang HC, Yang ZS, Yeh CS, Shieh DB, Su WC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e58bd7606997432f8ee6c7c34c5c3ad1
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spelling	oai:doaj.org-article:e58bd7606997432f8ee6c7c34c5c3ad12021-12-02T05:02:10ZNucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy1176-91141178-2013https://doaj.org/article/e58bd7606997432f8ee6c7c34c5c3ad12012-10-01T00:00:00Zhttp://www.dovepress.com/nucleocytoplasmic-transport-blockage-by-sv40-peptide-modified-gold-nan-a11203https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Tsung-Lin Tsai,1,5 Chia-Cheng Hou,1,5 Hao-Chen Wang,1,5 Zih-Syuan Yang,2 Chen-Sheng Yeh,4 Dar-Bin Shieh,2,3 Wu-Chou Su1,51Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Center for Micro/Nano Science and Technology, 4Department of Chemistry, National Cheng Kung University, Tainan, Taiwan; 5Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanAbstract: Gold nanoparticles modified with the nuclear localization signal from simian virus 40 large T antigen (GNP-PEG/SV40) accumulate on the cytoplasmic side of the nuclear membrane in HeLa cells. Accumulation of GNP-PEG/SV40 around the nucleus blocks nucleocytoplasmic transport and prevents RNA export and nuclear shuttling of signaling proteins. This long-term blockage of nucleocytoplasmic transport results in cell death. This cell death is not caused by apoptosis or necrosis because caspases 3 and 9 are not activated, and the expression of annexin V/propidium iodide is not enhanced in HeLa cells after treatment. Using transmission electron microscopy, autophagosomes and autolysosomes were seen to appear after 72 hours of treatment with GNP-PEG/SV40. Increasing levels of enhanced green fluorescent protein-microtubule-associated protein 1 light chain 3 (EGFP-LC3)-positive punctate and LC3-II confirmed GNP-PEG/SV40-induced autophagy. In SiHa cells, treatment did not induce accumulation of GNP-PEG/SV40 around the nucleus and autophagy. Treating cells with wheat germ agglutinin, a nuclear pore complex inhibitor, induced autophagy in both HeLa and SiHa cells. GNP-PEG/SV40-induced autophagy plays a role in cell death, not survival, and virus-mediated small hairpin RNA silencing of Beclin-1 attenuates cell death. Taken together, the results indicate that long-term blockade of nucleocytoplasmic transport results in autophagic cell death.Keywords: gold nanoparticles, nucleocytoplasmic transport blockage, autophagy, wheat germ agglutininTsai TLHou CCWang HCYang ZSYeh CSShieh DBSu WCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5215-5234 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tsai TL Hou CC Wang HC Yang ZS Yeh CS Shieh DB Su WC Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
description	Tsung-Lin Tsai,1,5 Chia-Cheng Hou,1,5 Hao-Chen Wang,1,5 Zih-Syuan Yang,2 Chen-Sheng Yeh,4 Dar-Bin Shieh,2,3 Wu-Chou Su1,51Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Center for Micro/Nano Science and Technology, 4Department of Chemistry, National Cheng Kung University, Tainan, Taiwan; 5Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanAbstract: Gold nanoparticles modified with the nuclear localization signal from simian virus 40 large T antigen (GNP-PEG/SV40) accumulate on the cytoplasmic side of the nuclear membrane in HeLa cells. Accumulation of GNP-PEG/SV40 around the nucleus blocks nucleocytoplasmic transport and prevents RNA export and nuclear shuttling of signaling proteins. This long-term blockage of nucleocytoplasmic transport results in cell death. This cell death is not caused by apoptosis or necrosis because caspases 3 and 9 are not activated, and the expression of annexin V/propidium iodide is not enhanced in HeLa cells after treatment. Using transmission electron microscopy, autophagosomes and autolysosomes were seen to appear after 72 hours of treatment with GNP-PEG/SV40. Increasing levels of enhanced green fluorescent protein-microtubule-associated protein 1 light chain 3 (EGFP-LC3)-positive punctate and LC3-II confirmed GNP-PEG/SV40-induced autophagy. In SiHa cells, treatment did not induce accumulation of GNP-PEG/SV40 around the nucleus and autophagy. Treating cells with wheat germ agglutinin, a nuclear pore complex inhibitor, induced autophagy in both HeLa and SiHa cells. GNP-PEG/SV40-induced autophagy plays a role in cell death, not survival, and virus-mediated small hairpin RNA silencing of Beclin-1 attenuates cell death. Taken together, the results indicate that long-term blockade of nucleocytoplasmic transport results in autophagic cell death.Keywords: gold nanoparticles, nucleocytoplasmic transport blockage, autophagy, wheat germ agglutinin
format	article
author	Tsai TL Hou CC Wang HC Yang ZS Yeh CS Shieh DB Su WC
author_facet	Tsai TL Hou CC Wang HC Yang ZS Yeh CS Shieh DB Su WC
author_sort	Tsai TL
title	Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
title_short	Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
title_full	Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
title_fullStr	Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
title_full_unstemmed	Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy
title_sort	nucleocytoplasmic transport blockage by sv40 peptide-modified gold nanoparticles induces cellular autophagy
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/e58bd7606997432f8ee6c7c34c5c3ad1
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Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy

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