Human blood cells support the reduction of low-density-lipoprotein-associated cholesteryl ester hydroperoxides by albumin-bound ebselen
Autor: | Roland Stocker, Helmut Sies, Julie K. Christison |
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Jazyk: | angličtina |
Rok vydání: | 1994 |
Předmět: |
Adult
Azoles Male Isoindoles Biochemistry chemistry.chemical_compound Organoselenium Compounds Extracellular Humans Molecular Biology Serum Albumin Whole blood chemistry.chemical_classification Glutathione Peroxidase Blood Cells Ebselen Glutathione peroxidase Albumin Cell Biology Cholesterol LDL Glutathione Dithiothreitol Cholesterol chemistry Low-density lipoprotein Cholesteryl ester Female Cholesterol Esters Oxidation-Reduction Lipoprotein Research Article |
Popis: | Ebselen, a glutathione peroxidase mimic capable of reducing simple as well as complex hydroperoxides, including those of phospholipids and cholesteryl esters in intact oxidized low-density lipoprotein (LDLox), requires the presence of low-molecular-mass thiols to be active. In plasma, the drug is thought to be transported as an inactive albumin complex. As formation of LDLox is likely to occur extracellularly, we tested under which conditions ebselen can support reduction of LDLox-associated cholesteryl ester hydroperoxides outside cells. We observed that addition of albumin-bound ebselen to whole blood, but not plasma, resulted in reduction of LDLox-associated cholesteryl linoleate hydroperoxides to the corresponding hydroxides. The observed reduction was rapid and its extent increased with increasing concentrations of ebselen. Physical contact of blood cells with LDLox was not required for this reducing activity. These results demonstrate that, in the presence of blood cells, extracellular ebselen is catalytically active. They suggest that ebselen may be considered as a drug for extracellular targets. |
Databáze: | OpenAIRE |
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