Yang Chul Woo, Li Can, Jung Ju Young, Shin Seok Joon, Choi Bum Soon, Lim Sun Woo, Sun Bo Kyung, Kim Yong Soo, Kim Jin, Chang Yoon Sik, Bang Byung Kee
Cell Death Disease Research Center, Department ofInternal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
FASEB J. 2003 Sep;17(12):1754-5. doi: 10.1096/fj.02-1191fje. Epub 2003 Jul 18.
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.
