Epoetin delta reduces oxidative stress in primary human renal tubular cells.
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.
De Beuf
Annelies
A
Laboratory of Pathophysiology, Faculties of Medicine and Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Hou
Xiang-hua
XH
D'Haese
Patrick C
PC
Verhulst
Anja
A
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
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
Kidney Int. 2004 Aug;66(2):683-95
15253723
Mutagenesis. 2008 Jul;23(4):293-8
18353768
Physiol Rev. 2002 Jan;82(1):205-44
11773613
J Mol Biol. 2004 Apr 23;338(2):257-69
15066430
Curr Opin Nephrol Hypertens. 2009 Jan;18(1):15-20
19077684
Clin Chim Acta. 2009 Jan;399(1-2):24-39
18957287
Biochim Biophys Acta. 2007 Feb;1774(2):267-77
17208058
Am J Physiol Renal Physiol. 2006 Mar;290(3):F563-71
16461755
Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94
12892317
In Vitro Cell Dev Biol. 1987 Apr;23(4):279-87
2437097
J Heart Lung Transplant. 2007 Feb;26(2):174-80
17258152
Free Radic Biol Med. 2002 Sep 1;33(5):691-702
12208356
EMBO Rep. 2002 Dec;3(12):1146-51
12475928
FASEB J. 2003 Sep;17(12):1754-5
12958199
Biochem Biophys Res Commun. 2007 Aug 10;359(4):928-34
17560935
J Biol Chem. 2007 Oct 12;282(41):30207-15
17673462
Arch Biochem Biophys. 2001 May 1;389(1):84-93
11370676
IUBMB Life. 2004 Nov-Dec;56(11-12):681-7
15804832
Curr Gastroenterol Rep. 2005 Aug;7(4):308-16
16042916
Biochem J. 1976 Jul 1;157(1):169-82
962853
Kidney Int Suppl. 2007 Nov;(107):S10-5
17943138
Hemoglobin. 2008;32(3):287-96
18473245
Oncogene. 2004 Nov 25;23(55):8987-91
15480420
Am J Respir Cell Mol Biol. 2009 Sep;41(3):251-60
19617398
Free Radic Res. 1995 Apr;22(4):375-83
7633567
Kidney Int. 2003 Apr;63(4):1564-73
12631374
J Am Soc Nephrol. 2004 Aug;15(8):2115-24
15284297
J Biol Chem. 1999 Oct 29;274(44):31632-40
10531371
Kidney Int. 1997 Aug;52(2):414-28
9263997
Exp Cell Res. 2003 Dec 10;291(2):386-97
14644160
J Neurosci Methods. 2007 Aug 15;164(1):50-8
17524492
Adv Exp Med Biol. 2007;618:169-80
18269196
Nephrol Dial Transplant. 2004 Feb;19(2):348-55
14736958
Mol Hum Reprod. 2003 Dec;9(12):799-806
14614042
Kidney Int. 2001 Feb;59(2):554-64
11168937
J Med Chem. 1999 Mar 25;42(6):1041-52
10090787
Biochem Pharmacol. 2008 Dec 15;76(12):1637-43
18755155
Cardiovasc Res. 2006 Sep 1;71(4):684-94
16828072
J Am Soc Nephrol. 2003 Mar;14(3):745-54
12595512
Mol Ther. 2006 Jun;13(6):1093-100
16581302
Biochim Biophys Acta. 2005 Aug 1;1751(1):26-32
15897020
J Heart Lung Transplant. 2006 Sep;25(9):1109-16
16962474