title: Cytochrome c-binding "proteo-dendrimers" as new types of apoptosis inhibitors working in HeLa cell systems.
abstract: 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..
authors.affiliation: Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka, 558-8585, Japan. azumah@bioa.eng.osaka-cu.ac.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Azuma
authors.forename: Yuuka
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Dharam
authors.initials: D
authors.lastname: Paul
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shinoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukube
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagasaki