Reference - Detail
|Author||Ishihara T, Nara S, Mizushima T.|
|Title||Interactions of lecithinized superoxide dismutase with serum proteins and cells.|
|Journal||J Pharm Sci|
Superoxide dismutase covalently bound to four lecithin molecules (PC-SOD) is known to be retained in circulating blood for a prolonged period and has a high affinity for cells, resulting in beneficial therapeutic effects in animal disease models. In this study, we evaluated the interaction of PC-SOD with biological components, such as serum proteins and cells, to clarify the mechanism underlying the improved pharmacokinetics of SOD induced by lecithin chemical modification (lecithinization). PC-SOD was distributed in the plasma but not in blood cells after being added to the blood. PC-SOD formed a complex with serum protein(s) such as albumin, whereas unmodified SOD did not. The cellular content of PC-SOD was markedly higher than that of unmodified SOD, and was distributed in lysosomes. The pathway associated with the cellular uptake was found to involve clathrin-/caveolae-independent and cholesterol-sensitive endocytosis. Overall, our data indicated that the increased hydrophobicity of lecithinized SOD enhanced its association to both serum protein(s) and plasma membrane microdomains. The former inhibited SOD excretion and promoted long-term retention in circulating blood, whereas the latter enhanced internalization into cells via endocytosis.
|MeSH||Animals Blood Proteins / chemistry* Cell Culture Techniques Cell Nucleus / drug effects Cell Nucleus / metabolism Chromatography, High Pressure Liquid Drug Delivery Systems Electrophoresis, Polyacrylamide Gel Endocytosis* / drug effects HeLa Cells Humans Hydrophobic and Hydrophilic Interactions Lysosomes / drug effects Lysosomes / metabolism Macrophages / drug effects Macrophages / metabolism Male Membrane Microdomains / drug effects Membrane Microdomains / metabolism Membrane Transport Proteins / metabolism Mice Phosphatidylcholines / administration & dosage Phosphatidylcholines / blood* Phosphatidylcholines / chemistry Phosphatidylcholines / pharmacology Rats, Wistar Superoxide Dismutase / administration & dosage Superoxide Dismutase / blood* Superoxide Dismutase / chemistry Superoxide Dismutase / pharmacology|
|WOS Category||PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL CHEMISTRY, MULTIDISCIPLINARY|
|Human and Animal Cells|