Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury: Gender differences

Ágnes Prókai, Andrea Fekete, Nóra Fanni Bánki, V. Müller, A. Vér, Péter Degrell, K. Rusai, L. Wágner, A. Vannay, Máté Rosta, Uwe Heemann, R. Langer, T. Tulassay, G. Reusz, Attila J. Szabó

Research output: Contribution to journalArticle

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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. Conclusion: 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.

Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalSurgery
Volume150
Issue number1
DOIs
Publication statusPublished - Jul 2011

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Erythropoietin
Reperfusion Injury
HSP72 Heat-Shock Proteins
Kidney
Reperfusion
Wounds and Injuries
Ischemia
rat erythropoietin
Membranes
sodium-translocating ATPase
Wistar Rats
Proteins

ASJC Scopus subject areas

  • Surgery

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Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury : Gender differences. / Prókai, Ágnes; Fekete, Andrea; Bánki, Nóra Fanni; Müller, V.; Vér, A.; Degrell, Péter; Rusai, K.; Wágner, L.; Vannay, A.; Rosta, Máté; Heemann, Uwe; Langer, R.; Tulassay, T.; Reusz, G.; Szabó, Attila J.

In: Surgery, Vol. 150, No. 1, 07.2011, p. 39-47.

Research output: Contribution to journalArticle

Prókai, Ágnes ; Fekete, Andrea ; Bánki, Nóra Fanni ; Müller, V. ; Vér, A. ; Degrell, Péter ; Rusai, K. ; Wágner, L. ; Vannay, A. ; Rosta, Máté ; Heemann, Uwe ; Langer, R. ; Tulassay, T. ; Reusz, G. ; Szabó, Attila J. / Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury : Gender differences. In: Surgery. 2011 ; Vol. 150, No. 1. pp. 39-47.
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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. Conclusion: 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.",
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T1 - Renoprotective effect of erythropoietin in rats subjected to ischemia/reperfusion injury

T2 - Gender differences

AU - Prókai, Ágnes

AU - Fekete, Andrea

AU - Bánki, Nóra Fanni

AU - Müller, V.

AU - Vér, A.

AU - Degrell, Péter

AU - Rusai, K.

AU - Wágner, L.

AU - Vannay, A.

AU - Rosta, Máté

AU - Heemann, Uwe

AU - Langer, R.

AU - Tulassay, T.

AU - Reusz, G.

AU - Szabó, Attila J.

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N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

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