title: Scavenging of superoxide anions by lecithinized superoxide dismutase in HL-60 cells.
abstract: Superoxide dismutase covalently bound to four lecithin molecules (PC-SOD) has been found to have beneficial therapeutic effects in animal models of various diseases. However, the mechanism underlying these improved therapeutic effects has not yet been elucidated. It has previously been shown that PC-SOD localizes on the plasma membrane and in the lysosomes of cells. In this study, we evaluated the superoxide anion-scavenging activity of PC-SOD in HL-60 human promyelocytic leukemia cells. Compared to SOD, PC-SOD had only 17% scavenging activity in cell-free systems. Nevertheless, by analyzing enzyme activities in cell suspensions containing PC-SOD or SOD, PC-SOD and SOD showed almost equal activity for scavenging extracellular superoxide anions produced by HL-60 cells. Furthermore, the activity for scavenging extracellular superoxide anions increased with increased amount of PC-SOD on the plasma membrane. Moreover, PC-SOD exhibited no obvious inhibitory effect on the scavenging of intracellular superoxide anions. These results suggested that the association of PC-SOD with the plasma membrane plays a key role in its beneficial therapeutic effects. Thus, this finding may provide a rationale for selecting target diseases for PC-SOD treatment.
authors.affiliation: Department of Chemical Biology and Applied Chemistry, College of Engineering, Nihon University, 1 Nakagawara, Tokusada, Tamuramachi, Koriyama, Fukushima 963-8642, Japan. ishihara@chem.ce.nihon-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Department of Chemical Biology and Applied Chemistry, College of Engineering, Nihon University, 1 Nakagawara, Tokusada, Tamuramachi, Koriyama, Fukushima 963-8642, Japan. ishihara@chem.ce.nihon-u.ac.jp.
authors.forename: Misaki
authors.initials: M
authors.lastname: Shibui
authors.affiliation: Department of Chemical Biology and Applied Chemistry, College of Engineering, Nihon University, 1 Nakagawara, Tokusada, Tamuramachi, Koriyama, Fukushima 963-8642, Japan. ishihara@chem.ce.nihon-u.ac.jp.
authors.forename: Takaya
authors.initials: T
authors.lastname: Hoshi
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000838:Anions / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000838:Anions; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D013481:Superoxides; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase