Interaction of albumin-bound ebselen with rat liver glutathione S-transferase and microsomal proteins.
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a selenium-containing heterocyclic compound, transported bound to albumin in blood. In this report, we demonstrate the transfer of ebselen from its albumin complex to rat liver cytosolic glutathione-S-transferase (GST) and microsomal proteins, as compared to papain. Free ebselen binds to the sulfhydryl groups of proteins, such as GST and papain [Nikawa, T., Schuch, G., Wagner, G. & Sies, H. Biochem. Pharmacol. (in press)]. 2-Mercaptoethanol and N-ethylmaleimide interfere with ebselen binding to microsomal proteins, suggesting that ebselen also binds to the sulfhydryl groups of microsomal proteins. Ebselen is transferred from its albumin complex to rat liver cytosolic GST and microsomal proteins, but not to papain. These results suggest the possibility that ebselen is transferred from albumin to other proteins using their sulfhydryl groups in vivo.
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
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Nikawa
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Schuch
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Wagner
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Sies
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D001393:Azoles / Q000097:blood* / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D054833:Isoindoles; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D016566:Organoselenium Compounds / Q000097:blood* / Q000378:metabolism; D010206:Papain / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D011506:Proteins; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; C042986:ebselen; D005982:Glutathione Transferase; D010206:Papain