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Int J Nanomedicine. 2012;7:5215-34. doi: 10.2147/IJN.S35125. Epub 2012 Oct 8.

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

Author information

1
Institute of Basic Medical Sciences, National Cheng Kung University, and Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

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:

autophagy; gold nanoparticles; nucleocytoplasmic transport blockage; wheat germ agglutinin

PMID:
23071392
PMCID:
PMC3469097
DOI:
10.2147/IJN.S35125
[Indexed for MEDLINE]
Free PMC Article
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