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Cationic liposomes induce macrophage apoptosis through mitochondrial pathway
Y Aramaki1, S Takano, S Tsuchiya
1School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. aramaki@ps.toyaku.ac.jp
Abstract:
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.
Insights
Cationic liposomes trigger apoptosis in macrophage cells via the mitochondrial pathway. Reactive oxygen species (ROS) generation is essential for this cell death process, involving mitochondrial membrane depolarization and cytochrome c release.
Area of Science:
- Cell Biology
- Biochemistry
- Toxicology
Background:
- Cationic liposomes are widely used in drug delivery systems.
- Understanding the mechanisms of liposome-induced cell death is crucial for safety assessment.
Purpose of the Study:
- To elucidate the mechanism of apoptosis induced by stearylamine-containing cationic liposomes (SA-liposomes) in RAW264.7 macrophage cells.
- To investigate the role of mitochondria and reactive oxygen species (ROS) in SA-liposome-induced apoptosis.
Main Methods:
- Treatment of RAW264.7 cells with SA-liposomes.
- Measurement of mitochondrial membrane potential.
- Analysis of cytochrome c release.
- Assessment of Caspase-3 activation.
- Evaluation of ROS generation using N-acetylcysteine.
Main Results:
- SA-liposomes induced mitochondrial membrane depolarization and cytochrome c release.
- SA-liposome treatment led to Caspase-3 activation.
- N-acetylcysteine pretreatment protected cells against SA-liposome-induced apoptosis, indicating the involvement of ROS.
Conclusions:
- SA-liposomes induce apoptosis in RAW264.7 cells through the mitochondrial pathway.
- ROS generation is a critical mediator of SA-liposome-induced apoptosis.