Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.
Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl-2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose-dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.
Yang
Chul Woo
CW
Cell Death Disease Research Center, Department ofInternal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Li
Can
C
Jung
Ju Young
JY
Shin
Seok Joon
SJ
Choi
Bum Soon
BS
Lim
Sun Woo
SW
Sun
Bo Kyung
BK
Kim
Yong Soo
YS
Kim
Jin
J
Chang
Yoon Sik
YS
Bang
Byung Kee
BK
D000818:Animals; D017209:Apoptosis; D004921:Erythropoietin / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D019194:Ischemic Preconditioning; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction
D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D020928:Mitogen-Activated Protein Kinases