title: Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury: gender differences.
abstract: BACKGROUND
  Renal ischemia reperfusion injury induces gender-dependent heat-shock protein 72 expression, which maintains membrane localization of renal Na(+)/K(+)ATPase-α1. The erythropoietin has a protecting effect against ischemia reperfusion injury in various organs. In this study, we investigated whether erythropoietin exerts a beneficial effect against post-ischemic renal injury. Furthermore, we studied the erythropoietin signaling on heat-shock protein 72 and Na(+)/K(+)ATPase-α1 expression and localization.
  
  
  METHODS
  In male and female Wistar rats, rHuEPO (1000 IU/bwkg intraperitoneal) or vehicle was administered 24 hours prior to unilateral left renal ischemia reperfusion (50 minutes). Kidneys were subsequently removed at hours 2 or 24 of the reperfusion; sham-operated rats served as controls (C) (n = 8/group). We measured serum erythropoietin, renal function, evaluated histological injury, and observed heat-shock protein 72 as well as Na(+)/K(+)ATPase-α1 protein level and localization. Additional groups were followed for 7-day survival.
  
  
  RESULTS
  Erythropoietin treatment was associated with better post-ischemic survival and less impaired renal function in males while diminishing the renal structural damage in both sexes. Endogenous erythropoietin was higher in males and increased in both genders after erythropoietin treatment. The erythropoietin treatment elevated protein levels of heat-shock protein 72 and Na(+)/K(+)ATPase-α1 in 24 hours in males, whereas in females, the already higher expression of heat-shock protein 72 and Na(+)/K(+)ATPase-α1 was not increased. Moreover, erythropoietin prevented ischemia reperfusion induced Na(+)/K(+)ATPase-α1 translocation from the basolaterale membrane in males.
  
  
  CONCLUSIONS
  Erythropoietin diminishes gender difference in the susceptibility to renal post-ischemic injury and reduces post-ischemic structural damage while preserving kidney function, particularly in males. This additional protection may be associated with a heat-shock protein 72-mediated effect on Na(+)/K(+)ATPase-α1 expression and translocation.
authors: First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors: Agnes
authors: A
authors: Prókai
authors: Andrea
authors: A
authors: Fekete
authors: Nóra Fanni
authors: NF
authors: Bánki
authors: Veronika
authors: V
authors: Müller
authors: Agota
authors: A
authors: Vér
authors: Péter
authors: P
authors: Degrell
authors: Krisztina
authors: K
authors: Rusai
authors: László
authors: L
authors: Wagner
authors: Adám
authors: A
authors: Vannay
authors: Máté
authors: M
authors: Rosta
authors: Uwe
authors: U
authors: Heemann
authors: Róbert M
authors: RM
authors: Langer
authors: Tivadar
authors: T
authors: Tulassay
authors: György
authors: G
authors: Reusz
authors: Attila J
authors: AJ
authors: Szabó