Artículo
Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion
Autor/es | Domínguez Rodríguez, Alejandro
Mayoral-González, Isabel Ávila Medina, Javier Sánchez de Rojas de Pedro, Eva Calderón Sánchez, Eva María Díaz Carrasco, Ignacio Hmadcha, Abdelkrim Castellano Orozco, Antonio Gonzalo Ordóñez Fernández, Antonio Smani Hajami, Tarik |
Departamento | Instituto de Biomedicina de Sevilla (IBIS) Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) |
Fecha de publicación | 2018-07-03 |
Fecha de depósito | 2018-08-21 |
Publicado en |
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Premios | Premio Anual Publicación Científica Destacada de la US. Facultad de Medicina |
Resumen | Aims: Urocortin-2 (Ucn-2) is a potent cardioprotector against Ischemia and Reperfusion (I/R) injuries. However, little is known about its role in the regulation of intracellular Ca2+ concentration ([Ca2+]i) under I/R. Here, ... Aims: Urocortin-2 (Ucn-2) is a potent cardioprotector against Ischemia and Reperfusion (I/R) injuries. However, little is known about its role in the regulation of intracellular Ca2+ concentration ([Ca2+]i) under I/R. Here, we examined whether the addition of Ucn-2 in reperfusion promotes cardioprotection focusing on ([Ca2+]i handling. Methods and Results: Cardiac Wistar rat model of I/R was induced by transient ligation of the left coronary artery and experiments were conducted 1 week after surgery in tissue and adult cardiomyocytes isolated from risk and remote zones. We observed that I/R promoted significant alteration in cardiac contractility as well as an increase in hypertrophy and fibrosis in both zones. The study of confocal [Ca2+]i imaging in adult cardiomyocytes revealed that I/R decreased the amplitude of [Ca2+]i transient and cardiomyocytes contraction in risk and remote zones. Interestingly, intravenous infusion of Ucn-2 before heart’s reperfusion recovered significantly cardiac contractility and prevented fibrosis, but it didn’t affect cardiac hypertrophy. Moreover, Ucn-2 recovered the amplitude of [Ca2+]i transient and modulated the expression of several proteins related to [Ca2+]i homeostasis, such as TRPC5 and Orai1 channels. Using Neonatal Rat Ventricular Myocytes (NRVM) we demonstrated that Ucn-2 blunted I/R-induced Store Operated Ca2+ Entry (SOCE), decreased the expression of TRPC5 and Orai1 as well as their interaction in reperfusion. Conclusion: Our study provides the first evidences demonstrating that Ucn-2 addition at the onset of reperfusion attenuates I/R-induced adverse cardiac remodeling, involving the [Ca2+]i handling and inhibiting the expression and interaction between TRPC5 and Orai1. |
Identificador del proyecto | 316151
BFU2016-74932-C2 BFU2013-45564-C2 PI15/00203 PI16/00259 CB16/11/00431 P12-CTS-1965 PI-0313-2016 PI-0108-2012 P12-CTS-1965 PI-0313-2016 ANR-13-BSVI-0023-01 |
Cita | Domínguez Rodríguez, A., Mayoral-González, I., Ávila Medina, J., Sánchez de Rojas de Pedro, E., Calderón Sánchez, E.M., Díaz Carrasco, I.,...,Smani Hajami, T. (2018). Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion. Frontiers in Physiology, 9, 813-1-813-16. https://doi.org/10.3389/fphys.2018.00813. |
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