title: Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.
abstract: 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.
authors.affiliation: Cell Death Disease Research Center, Department ofInternal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Sun
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Chang
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
mesh_terms: 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
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D020928:Mitogen-Activated Protein Kinases