期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 7, 期 8, 页码 1700-1704出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/b900154a
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资金
- Suzuken Memorial Foundation
The suppressive effects of synthetic dendrimers on mitochondrial apoptosis were first demonstrated in human epithelial carcinoma HeLa cells. The employed proteo-dendrimers included polyanionic hepta( glutamic acids), a fluorescent zinc porphyrinate core, hydrophilic polyether surface and nonpeptide hydrophobic dendrons, and electrostatically interacted with cytochrome c in aqueous solutions. The ceramide analogue, (2S,4E)-2-acetylamino-3-oxo-4-octadecen-1-ol (C2-ketoCer) induced mitochondrial apoptosis into HeLa cells and the cell viability was significantly recovered by pretreatment with some dendrimers. Among a series of proteo-dendrimers, the second-generation dendrimer 2a had the lowest cytotoxicity and the highest solubility. When the cells were treated with this dendrimer, a decrease in the protein levels of active caspase-3 and proteolytically cleaved PARP was remarkably observed. Since cytochrome c release from the mitochondria to the cytoplasm was unaffected in the presence of dendrimer 2a, the observed suppressive effects probably indicate that the proteo-dendrimer trapped cytochrome c, not only in the aqueous solutions but also in the living cells.
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