Cytochrome c-binding "proteo-dendrimers" as new types of apoptosis inhibitors working in HeLa cell systems.
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..
Azuma
Hideki
H
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
Yoshida
Yuuka
Y
Paul
Dharam
D
Shinoda
Satoshi
S
Tsukube
Hiroshi
H
Nagasaki
Takeshi
T