title: Changes in redox affect the activity of erythropoietin RNA binding protein.
abstract: We have previously identified a cytosolic protein, erythropoietin RNA binding protein (ERBP), which is up-regulated in certain tissues in response to hypoxia. To further characterize the interaction of ERBP and erythropoietin (EPO) mRNA, we have examined the role of reduction-oxidation in the EPO mRNA binding mechanism of ERBP isolated from human hepatoma cells (Hep3B). Reducing agents dithiothreitol (DTT) and 2-mercaptoethanol (2-ME) increased ERBP binding activity in a concentration-dependent manner, whereas the oxidizing agent, diamide, abolished ERBP binding activity. In addition, treatment of Hep3B cell lysates with the irreversible sulfhydryl alkylating agent N-ethylmaleimide resulted in inhibition of the EPO mRNA-ERBP complex. Taken together, these findings suggest that sulfhydryl groups may play a role in vivo in the regulation of EPO production through the modulation of ERBP binding activity.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
authors.forename: I J
authors.initials: IJ
authors.lastname: Rondon
authors.forename: A B
authors.initials: AB
authors.lastname: Scandurro
authors.forename: R B
authors.initials: RB
authors.lastname: Wilson
authors.forename: B S
authors.initials: BS
authors.lastname: Beckman
mesh_terms: D015687:Cell Hypoxia; D004921:Erythropoietin / Q000235:genetics*; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016877:Oxidants; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D004921:Erythropoietin; D005033:Ethylmaleimide