RGD Reference Report - Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta. - Rat Genome Database

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Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta.

Authors: Nishihara, M  Miura, T  Miki, T  Sakamoto, J  Tanno, M  Kobayashi, H  Ikeda, Y  Ohori, K  Takahashi, A  Shimamoto, K 
Citation: Nishihara M, etal., Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H748-55. Epub 2006 Mar 24.
RGD ID: 10045368
Pubmed: PMID:16565311   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00837.2005   (Journal Full-text)

The aim of this study was to determine whether erythropoietin (EPO) affords additional cardioprotection to the preconditioned myocardium by enhanced phosphorylation of Akt, STAT3, or glycogen synthase kinase-3beta (GSK-3 beta). Preconditioning (PC) with 5-min ischemia/5-min reperfusion and EPO (5,000 U/kg iv) reduced infarct size (as % of area at risk, %IS/AR) after 20-min ischemia in rat hearts in situ from 56.5 +/- 1.8% to 25.2 +/- 2.1% and to 36.2 +/- 2.8%, respectively. PC-induced protection was significantly inhibited by a protein kinase C inhibitor, chelerythrine (5 mg/kg), and slightly blunted by a phosphatidylinositol-3-kinase inhibitor, wortmannin (15 microg/kg). The opposite pattern of inhibition was observed for EPO-induced protection. The combination of PC and EPO further reduced %IS/AR to 8.9 +/- 1.9%, and this protection was inhibited by chelerythrine and wortmannin. The additive effects of PC and EPO on infarct size were mirrored by their effects on the level of phosphorylated GSK-3 beta at 5 min after reperfusion but not their effects on the level of phospho-Akt or phospho-STAT3. To mimic phosphorylation-induced inhibition of GSK-3 beta activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before ischemia or 5 min before reperfusion. Infarct size was significantly reduced by preischemic injection (%IS/AR = 40.4 +/- 2.2% by 0.6 mg/kg SB and 34.0 +/- 1.8% by 1.2 mg/kg SB) and also by prereperfusion injection (%IS/AR = 32.0 +/- 2.0% by 1.2 mg/kg SB). These results suggest that EPO and PC afford additive infarct size-limiting effects by additive phosphorylation of GSK-3beta at the time of reperfusion by Akt-dependent and -independent mechanisms.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GSK3BHumanmyocardial infarction treatmentISOGsk3b (Rattus norvegicus) RGD 
Gsk3bRatmyocardial infarction treatmentIMP  RGD 
Gsk3bMousemyocardial infarction treatmentISOGsk3b (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Mus musculus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Homo sapiens)
GSK3B  (glycogen synthase kinase 3 beta)


Additional Information