Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human Cardiomyocytes

Aims: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. Methods and results: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 3...

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Detalles Bibliográficos
Autores: Tarazón, Estefanía, Rivera, Miguel, Roselló-Lletí, Esther, Molina-Navarro, Maria Micaela, Sánchez-Lázaro, Ignacio José, España, Francisco, Montero, José Anastasio, Lago Paz, Francisca, González Juanatey, José Ramón, Portolés, Manuel
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/4826
Acceso en línea:http://hdl.handle.net/20.500.11940/4826
Access Level:acceso abierto
Palabra clave:Heart Failure
Heart Ventricles
Myocytes, Cardiac
Nuclear Pore Complex Proteins
Insuficiencia Cardíaca
Ventrículos Cardíacos
Miocitos Cardíacos
Proteínas de Complejo Poro Nuclear
Descripción
Sumario:Aims: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. Methods and results: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively). Conclusions: This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management.