Cationic liposomes induce macrophage apoptosis through mitochondrial pathway.
To clarify the mechanism of apoptosis of the macrophage-like cell line RAW264.7 induced by cationic liposomes, we focused on the mitochondria and investigated the changes in mitochondrial membrane potential and the release of cytochrome c following treatment of cationic liposomes composed of stearylamine (SA-liposomes). SA-liposomes induced mitochondrial membrane depolarization and also the release of cytochrome c from mitochondria. Caspase-3 was also activated by SA-liposome treatment. Pretreatment of cells with N-acetylcysteine, a scavenger of reactive oxygen species (ROS), conferred resistance to the induction of the membrane depolarization, cytochrome c release, and caspase-3 activation by SA-liposomes. These results indicated that SA-liposomes caused the apoptosis in RAW264.7 cells through the mitochondrial pathway, and ROS generation was required for this phenomenon.
Aramaki
Y
Y
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. aramaki@ps.toyaku.ac.jp
Takano
S
S
Tsuchiya
S
S
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002412:Cations; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*
D017304:Annexin A5; D002412:Cations; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D008081:Liposomes; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D000111:Acetylcysteine