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Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling.
Basic Res Cardiol. 2011 Jan; 106(1):147-62.BR

Abstract

Recent studies reported cardioprotective effects of erythropoietin (EPO) against ischemia-reperfusion (I/R) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been reported to be impaired in diabetes and insulin resistance syndrome, we examined whether EPO-induced cardioprotection was maintained in rat models of type 1 diabetes and insulin resistance syndrome. Isolated hearts were obtained from three rat cohorts: healthy controls, streptozotocin (STZ)-induced diabetes, and high-fat diet (HFD)-induced insulin resistance syndrome. All hearts underwent 25 min ischemia and 30 min or 120 min reperfusion. They were assigned to receive either no intervention or a single dose of EPO at the onset of reperfusion. In hearts from healthy controls, EPO decreased infarct size (14.36 ± 0.60 and 36.22 ± 4.20% of left ventricle in EPO-treated and untreated hearts, respectively, p < 0.05) and increased phosphorylated forms of Akt, ERK1/2, and their downstream target GSK-3β. In hearts from STZ-induced diabetic rats, EPO did not decrease infarct size (32.05 ± 2.38 and 31.88 ± 1.87% in EPO-treated and untreated diabetic rat hearts, respectively, NS) nor did it increase phosphorylation of Akt, ERK1/2, and GSK-3β. In contrast, in hearts from HFD-induced insulin resistance rats, EPO decreased infarct size (18.66 ± 1.99 and 34.62 ± 3.41% in EPO-treated and untreated HFD rat hearts, respectively, p < 0.05) and increased phosphorylation of Akt, ERK1/2, and GSK-3β. Administration of GSK-3β inhibitor SB216763 was cardioprotective in healthy and diabetic hearts. STZ-induced diabetes abolished EPO-induced cardioprotection against I/R injury through a disruption of upstream signaling of GSK-3β. In conclusion, direct inhibition of GSK-3β may provide an alternative strategy to protect diabetic hearts against I/R injury.

Authors+Show Affiliations

Protection et Remodelage du Myocarde, UPRES EA 3860, Faculté de Médecine, Université d'Angers, Rue Haute de Reculée, 49045 Angers Cedex 1, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20981553

Citation

Ghaboura, Nehmat, et al. "Diabetes Mellitus Abrogates Erythropoietin-induced Cardioprotection Against Ischemic-reperfusion Injury By Alteration of the RISK/GSK-3β Signaling." Basic Research in Cardiology, vol. 106, no. 1, 2011, pp. 147-62.
Ghaboura N, Tamareille S, Ducluzeau PH, et al. Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. Basic Res Cardiol. 2011;106(1):147-62.
Ghaboura, N., Tamareille, S., Ducluzeau, P. H., Grimaud, L., Loufrani, L., Croué, A., Tourmen, Y., Henrion, D., Furber, A., & Prunier, F. (2011). Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. Basic Research in Cardiology, 106(1), 147-62. https://doi.org/10.1007/s00395-010-0130-3
Ghaboura N, et al. Diabetes Mellitus Abrogates Erythropoietin-induced Cardioprotection Against Ischemic-reperfusion Injury By Alteration of the RISK/GSK-3β Signaling. Basic Res Cardiol. 2011;106(1):147-62. PubMed PMID: 20981553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. AU - Ghaboura,Nehmat, AU - Tamareille,Sophie, AU - Ducluzeau,Pierre-Henri, AU - Grimaud,Linda, AU - Loufrani,Laurent, AU - Croué,Anne, AU - Tourmen,Yves, AU - Henrion,Daniel, AU - Furber,Alain, AU - Prunier,Fabrice, Y1 - 2010/10/28/ PY - 2010/04/24/received PY - 2010/10/20/accepted PY - 2010/10/18/revised PY - 2010/10/29/entrez PY - 2010/10/29/pubmed PY - 2011/4/19/medline SP - 147 EP - 62 JF - Basic research in cardiology JO - Basic Res Cardiol VL - 106 IS - 1 N2 - Recent studies reported cardioprotective effects of erythropoietin (EPO) against ischemia-reperfusion (I/R) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been reported to be impaired in diabetes and insulin resistance syndrome, we examined whether EPO-induced cardioprotection was maintained in rat models of type 1 diabetes and insulin resistance syndrome. Isolated hearts were obtained from three rat cohorts: healthy controls, streptozotocin (STZ)-induced diabetes, and high-fat diet (HFD)-induced insulin resistance syndrome. All hearts underwent 25 min ischemia and 30 min or 120 min reperfusion. They were assigned to receive either no intervention or a single dose of EPO at the onset of reperfusion. In hearts from healthy controls, EPO decreased infarct size (14.36 ± 0.60 and 36.22 ± 4.20% of left ventricle in EPO-treated and untreated hearts, respectively, p < 0.05) and increased phosphorylated forms of Akt, ERK1/2, and their downstream target GSK-3β. In hearts from STZ-induced diabetic rats, EPO did not decrease infarct size (32.05 ± 2.38 and 31.88 ± 1.87% in EPO-treated and untreated diabetic rat hearts, respectively, NS) nor did it increase phosphorylation of Akt, ERK1/2, and GSK-3β. In contrast, in hearts from HFD-induced insulin resistance rats, EPO decreased infarct size (18.66 ± 1.99 and 34.62 ± 3.41% in EPO-treated and untreated HFD rat hearts, respectively, p < 0.05) and increased phosphorylation of Akt, ERK1/2, and GSK-3β. Administration of GSK-3β inhibitor SB216763 was cardioprotective in healthy and diabetic hearts. STZ-induced diabetes abolished EPO-induced cardioprotection against I/R injury through a disruption of upstream signaling of GSK-3β. In conclusion, direct inhibition of GSK-3β may provide an alternative strategy to protect diabetic hearts against I/R injury. SN - 1435-1803 UR - https://www.unboundmedicine.com/medline/citation/20981553/Diabetes_mellitus_abrogates_erythropoietin_induced_cardioprotection_against_ischemic_reperfusion_injury_by_alteration_of_the_RISK/GSK_3β_signaling_ L2 - https://dx.doi.org/10.1007/s00395-010-0130-3 DB - PRIME DP - Unbound Medicine ER -