The role of singlet oxygen in ischemia-reperfusin injury : the study using laser scanning confocal microscopy and electron paramagnetic resinance

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To elucidate the role of singlet oxygen in ischemia-reperfusion injury, the following studies were performed.1)The generation and quenching of singlet oxygen were chemically examined. When the solution including 6-formylpterin (6FP) was irradiated by fluorescent llight, singlet oxygen was generated, which was quenched by N-acetyl-L-cystein (NAC), glutathine (GSH) and histidine.2)The biological effects of photochemically generated singlet oxygen against were examined using rat hepatocytes. When the hepatocyted were loaded with 6FP and then irradiated by fluorescent llight, the cell death was induced, which was attenuated by the pre-treatment with NAC and GSH, but not with histidine.3)The effects of reactive oxygen species (ROS) generated by 6FP on the drug-induced cell injury were examined. When the rat hepatocytes were loaded with tumor necrosis factor-α and actinomycin D, the apoptotic cell injury was induced, which was attenuated by the pre-treatment with 6FP. The generated ROS by 6FP was thought to suppress the caspase activity and attenuated the apoptotic cell injury.4)The photodynamic effects of a novel pterin derivative were examined using a human pancreatic cancer cell line, Panc-1 cells. When the cells were loaded with the novel pterin and irradiated by ultraviolet (UV-A), the cell death was induced. The singlet oxygen generated during irradiation was thought to cause the cell death.5)The effects of 6FP on the heat-induced apoptosis were examined using a human leukemia cell line, U937 cells. When the cells were loaded with 6FP and exposed to heat shock (44℃ for 20 min), the apoptotic cell death was enhanced. The hydrogen peroxide generated by 6FP was thought to cause the enhancement.6)Lipopolysaccharide (LPS)-induced ROS generation and changes in glutathione level and their relation to the maturation of dendritic cells were examined. It was revealed that the ROS was involved in the cytokine production.