標題: Water-soluble germanium nanoparticles cause necrotic cell death and the damage can be attenuated by blocking the transduction of necrotic signaling pathway
作者: Ma, Yu-Hsin
Huang, Chin-Ping
Tsai, Jia-Shiuan
Shen, Mo-Yuan
Li, Yaw-Kuen
Lin, Lih-Yuan
應用化學系
Department of Applied Chemistry
關鍵字: Water-soluble germanium nanoparticles;Cytotoxicity;Calcium;Reactive oxygen species;Mitochondrial membrane potential;Necrosis
公開日期: 15-十二月-2011
摘要: Water-soluble germanium nanoparticles (wsGeNPs) with allyamine-conjugated surfaces were fabricated and emit blue fluorescence under ultraviolet light. The wsGeNP was physically and chemically stable at various experimental conditions. Cytotoxicity of the fabricated wsGeNP was examined. KIT assay demonstrated that wsGeNP possessed high toxicity to cells and clonogenic survival assay further indicated that this effect was not resulted from retarding cell growth. Flow cytometric analysis indicated that wsGeNP did not alter the cell cycle profile but the sub-G1 fraction was absent from treated cells. Results from DNA fragmentation and propidium iodide exclusion assays also suggested that apoptotic cell death did not occur in cells treated with wsGeNP. Addition of a necrosis inhibitor, necrostatin-1, attenuated cell damage and indicated that wsGeNP caused necrotic cell death. Cell signaling leads to necrotic death was investigated. Intracellular calcium and reactive oxygen species (ROS) levels were increased upon wsGeNP treatment. These effects can be abrogated by BAPTA-AM and N-acetyl cysteine respectively, resulting in a reduction in cell damage. In addition, wsGeNP caused a decrease in mitochondrial membrane potential (MMP) which could be recovered by cyclosporine A The cellular signaling events revealed that wsGeNP increase the cellular calcium level which enhances the production of ROS and leads to a reduction of MMP, consequentially results in necrotic cell death. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.toxlet.2011.09.018
http://hdl.handle.net/11536/14895
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2011.09.018
期刊: TOXICOLOGY LETTERS
Volume: 207
Issue: 3
起始頁: 258
結束頁: 269
顯示於類別:期刊論文


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