PMID- 19766721
OWN - NLM
STAT- MEDLINE
DCOM- 20100408
LR  - 20151119
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 61
IP  - 1
DP  - 2010 Jan
TI  - Antiapoptotic properties of recombinant human erythropoietin protects against 
      tubular cyclosporine toxicity.
PG  - 71-5
LID - 10.1016/j.phrs.2009.08.010 [doi]
AB  - During the early post transplant period, the tubular epithelium is the main 
      target of injuries including ischemia reperfusion and toxicity effects from 
      calcineurin inhibitors. Taking into account the tissue protective effects of 
      erythropoietin mediated through its antiapoptotic properties, we tested whether 
      administration of recombinant human erythropoietin protects against acute 
      cyclosporine nephrotoxicity. Four groups of five rats were intraperitoneally 
      treated over 28 days with 100UI/Kg/48h Epoetin beta (15mg/kg/day CsA diluted in 
      olive oil, 100UI/Kg/48h Epoetin beta+15mg/kg/day CsA, or olive oil. Histological 
      changes due to tubular necrosis were evaluated with Masson'Trichrome staining. 
      Apoptotic nuclei in kidneys were detected using the Terminal deoxynucleotidyl 
      Transferase Biotin-dUTP Nick End Labeling (TUNEL) method. Phospho-Akt, Akt, 
      cleaved caspase 3 and non cleaved caspase 3 expression were evaluated using 
      immunblotting. We demonstrate that recombinant human erythropoietin (epoetin 
      beta) improves renal function and protects against acute tubular injury. Our data 
      suggest that this nephroprotective effect is mediated by Akt activation and 
      inhibition of tubular apoptosis. Indeed, western blotting analysis of caspase 3 
      cleavage and Akt phosphorylation demonstrates that rhEPO activate Akt signaling 
      and inhibits caspase 3 cleavage induced by CsA. TUNEL staining confirms that 
      rhEPO inhibits CsA-induced tubular apoptosis. In conclusion, we describe here a 
      new potential target of recombinant human erythropoietin and our results provide 
      an interesting framework for further nephroprotective therapies based on 
      recombinant human erythropoietin.
CI  - Copyright 2009 Elsevier Ltd. All rights reserved.
FAU - Pallet, Nicolas
AU  - Pallet N
AD  - INSERM U775 and Universite Paris Descartes, Paris, France. 
      nicolas.pallet@univ-paris5.fr
FAU - Bouvier, Nicolas
AU  - Bouvier N
FAU - Legendre, Christophe
AU  - Legendre C
FAU - Beaune, Philippe
AU  - Beaune P
FAU - Thervet, Eric
AU  - Thervet E
FAU - Choukroun, Gabriel
AU  - Choukroun G
FAU - Martinez, Frank
AU  - Martinez F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090918
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Biomarkers)
RN  - 0 (Protective Agents)
RN  - 0 (Recombinant Proteins)
RN  - 0 (epoetin beta)
RN  - 11096-26-7 (Erythropoietin)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Biomarkers/blood
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - Creatinine/blood
MH  - Cyclosporine
MH  - Cytoprotection
MH  - Disease Models, Animal
MH  - Erythropoietin/*pharmacology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Kidney Cortex Necrosis/chemically induced/pathology/*prevention & control
MH  - Kidney Tubules/*drug effects/pathology
MH  - Male
MH  - Necrosis
MH  - Phosphorylation
MH  - Protective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins
MH  - Signal Transduction/drug effects
EDAT- 2009/09/22 06:00
MHDA- 2010/04/09 06:00
CRDT- 2009/09/22 06:00
PHST- 2009/07/17 00:00 [received]
PHST- 2009/08/09 00:00 [revised]
PHST- 2009/08/30 00:00 [accepted]
PHST- 2009/09/22 06:00 [entrez]
PHST- 2009/09/22 06:00 [pubmed]
PHST- 2010/04/09 06:00 [medline]
AID - S1043-6618(09)00241-2 [pii]
AID - 10.1016/j.phrs.2009.08.010 [doi]
PST - ppublish
SO  - Pharmacol Res. 2010 Jan;61(1):71-5. doi: 10.1016/j.phrs.2009.08.010. Epub 2009 
      Sep 18.