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

Tsung Lin Tsai, Chia Cheng Hou, Hao Chen Wang, Zih Syuan Yang, Chen Sheng Yeh, Dar Bin Shieh, Wu Chou Su

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)5215-5234
頁數20
期刊International journal of nanomedicine
7
DOIs
出版狀態Published - 2012

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物工程
  • 生物材料
  • 藥學科學
  • 藥物發現
  • 有機化學

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