title: Epoetin delta reduces oxidative stress in primary human renal tubular cells.
abstract: Erythropoietin (EPO) exerts (renal) tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs) from oxidative stress and if so which pathways are involved. EPO (epoetin delta) could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR) since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1), aquaporin-1 (AQP-1), and B-cell CLL/lymphoma 2 (Bcl-2) have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPPIV), and cytoglobin (Cygb) to play a role in this process.
authors.affiliation: Laboratory of Pathophysiology, Faculties of Medicine and Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: De Beuf
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Hou
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
authors.forename: Anja
authors.initials: A
authors.lastname: Verhulst
mesh_terms: D002478:Cells, Cultured; D000078842:Cytoglobin; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D005914:Globins / Q000235:genetics / Q000378:metabolism; D005949:Glucose Oxidase; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D020011:Protective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D058851:GPI-Linked Proteins; D020011:Protective Agents; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; C516023:epoetin delta; D000068817:Epoetin Alfa; D005914:Globins; D005949:Glucose Oxidase; D018819:Dipeptidyl Peptidase 4; C058479:carboxypeptidase M; D008666:Metalloendopeptidases
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