| Influence of heart failure on nucleocytoplasmic transport in human cardiomyocytes. | |
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MedLine Citation:
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PMID: 19819881 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: The role of the cell nucleus in the development of heart failure (HF) is unknown, so the objectives of this study were to analyse the effect of HF on nucleocytoplasmic transport and density of the nuclear pore complex (NPC). METHODS AND RESULTS: A total of 51 human heart samples from ischaemic (ICM, n = 30) and dilated (DCM, n = 16) patients undergoing heart transplantation and control donors (CNT, n = 5) were analysed by western blotting. Subcellular distribution of proteins and NPC were analysed by fluorescence and electron microscopy, respectively. When we compared nucleocytoplasmic machinery protein levels according to aetiology of HF, ICM showed higher levels of importins [(IMP-beta3) (150%, P < 0.0001), IMP-alpha2 (69%, P = 0.001)] and exportins [EXP-1 (178%, P < 0.0001), EXP-4 (81%, P = 0.006)] than those of the CNT group. Furthermore, DCM also showed significant differences for IMP-beta3 (192%, P < 0.0001), IMP-alpha2 (52%, P = 0.025), and EXP-1 (228%, P < 0.0001). RanGTPase-activating proteins (RanGAP1 and RaGAP1u) were increased in ICM (76%, P = 0.005; 51%, P = 0.012) and DCM (41%, P = 0.042; 50%, P = 0.029). Furthermore, subcellular distribution of nucleocytoplasmic machinery was not altered in pathological hearts. Finally, nucleoporin (Nup) p62 was increased in ICM (80%) and DCM (109%) (P < 0.001 and P = 0.024). Nuclear pore density was comparable in pathological and CNT hearts, and ICM showed a low diameter (P = 0.005) and different structural configuration of NPC. CONCLUSION: This study shows the effect of HF on nucleocytoplasmic trafficking machinery, evidenced by higher levels of importins, exportins, Ran regulators and Nup p62 in ischaemic and dilated human hearts than those in the controls, with NPCs acquiring a different configuration and morphology in ICM. |
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Authors:
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Raquel Cortés; Esther Roselló-Lletí; Miguel Rivera; Luis Martínez-Dolz; Antonio Salvador; Inmaculada Azorín; Manuel Portolés |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-09 |
Journal Detail:
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Title: Cardiovascular research Volume: 85 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-06 Completed Date: 2010-03-10 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 464-72 Citation Subset: IM |
Affiliation:
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Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Adult Aged Cell Nucleus / metabolism* Female GTPase-Activating Proteins / analysis Heart Failure / metabolism* Humans Male Middle Aged Myocytes, Cardiac / metabolism* Nuclear Pore / metabolism RNA-Binding Proteins / analysis beta Karyopherins / analysis |
| Chemical | |
Reg. No./Substance:
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0/GTPase-Activating Proteins; 0/IPO5 protein, human; 0/P62 protein, human; 0/RANGAP1 protein, human; 0/RNA-Binding Proteins; 0/beta Karyopherins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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