Lipoxygenase may be involved in cationic liposome-induced macrophage apoptosis.
The purpose of this study was to determine the source of reactive oxygen species (ROS) generation and the contribution of ROS to the apoptosis of RAW264.7 cells induced by cationic liposomes. Cationic liposome-induced apoptosis was inhibited by lipoxygenase inhibitors, but not inhibitors of NADPH-oxidase, xanthine oxidase or cyclooxygenase. ROS generation induced by cationic liposomes was also inhibited by the lipoxygenase inhibitor NDGA. Furthermore, lipid peroxidation was observed following liposome treatment, but the apoptosis was not inhibited by the antioxidant alpha-tocopherol. These findings suggested that lipoxygenase is responsible for ROS generation, and ROS but not lipid peroxidation acts as a key mediator in the progress of apoptosis induced by cationic liposomes.
Takano
S
S
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Aramaki
Y
Y
Tsuchiya
S
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology; D002412:Cations; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation; D008081:Liposomes; D008084:Lipoxygenase / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002412:Cations; D004791:Enzyme Inhibitors; D008081:Liposomes; D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D008084:Lipoxygenase