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Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance
Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveola...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774711/ https://www.ncbi.nlm.nih.gov/pubmed/24066022 http://dx.doi.org/10.1371/journal.pone.0071100 |
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author | Alcalay, Yifat Hochhauser, Edith Kliminski, Vitaly Dick, Julia Zahalka, Muayad A. Parnes, Doris Schlesinger, Hadassa Abassi, Zaid Shainberg, Asher Schindler, Roland F. R. Brand, Thomas Kessler-Icekson, Gania |
author_facet | Alcalay, Yifat Hochhauser, Edith Kliminski, Vitaly Dick, Julia Zahalka, Muayad A. Parnes, Doris Schlesinger, Hadassa Abassi, Zaid Shainberg, Asher Schindler, Roland F. R. Brand, Thomas Kessler-Icekson, Gania |
author_sort | Alcalay, Yifat |
collection | PubMed |
description | Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveolae and play a role in myocardial ischemia tolerance. To address these issues, we analyzed hearts and cardiomyocytes of wild type and Popdc1-null mice. Immunoconfocal microscopy revealed co-localization of Popdc1 with caveolin3 in the sarcolemma, intercalated discs and T-tubules and with costameric vinculin. Popdc1 was co-immunoprecipitated with caveolin3 from cardiomyocytes and from transfected COS7 cells and was co-sedimented with caveolin3 in equilibrium density gradients. Caveolae disruption by methyl-β-cyclodextrin or by ischemia/reperfusion (I/R) abolished the cellular co-localization of Popdc1 with caveolin3 and modified their density co-sedimentation. The caveolin3-rich fractions of Popdc1-null hearts redistributed to fractions of lower buoyant density. Electron microscopy showed a statistically significant 70% reduction in caveolae number and a 12% increase in the average diameter of the remaining caveolae in the mutant hearts. In accordance with these changes, Popdc1-null cardiomyocytes displayed impaired [Ca(+2)](i) transients, increased vulnerability to oxidative stress and no pharmacologic preconditioning. In addition, induction of I/R injury to Langendorff-perfused hearts indicated a significantly lower functional recovery in the mutant compared with wild type hearts while their infarct size was larger. No improvement in functional recovery was observed in Popdc1-null hearts following ischemic preconditioning. The results indicate that Popdc1 is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity and for heart protection. |
format | Online Article Text |
id | pubmed-3774711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37747112013-09-24 Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance Alcalay, Yifat Hochhauser, Edith Kliminski, Vitaly Dick, Julia Zahalka, Muayad A. Parnes, Doris Schlesinger, Hadassa Abassi, Zaid Shainberg, Asher Schindler, Roland F. R. Brand, Thomas Kessler-Icekson, Gania PLoS One Research Article Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveolae and play a role in myocardial ischemia tolerance. To address these issues, we analyzed hearts and cardiomyocytes of wild type and Popdc1-null mice. Immunoconfocal microscopy revealed co-localization of Popdc1 with caveolin3 in the sarcolemma, intercalated discs and T-tubules and with costameric vinculin. Popdc1 was co-immunoprecipitated with caveolin3 from cardiomyocytes and from transfected COS7 cells and was co-sedimented with caveolin3 in equilibrium density gradients. Caveolae disruption by methyl-β-cyclodextrin or by ischemia/reperfusion (I/R) abolished the cellular co-localization of Popdc1 with caveolin3 and modified their density co-sedimentation. The caveolin3-rich fractions of Popdc1-null hearts redistributed to fractions of lower buoyant density. Electron microscopy showed a statistically significant 70% reduction in caveolae number and a 12% increase in the average diameter of the remaining caveolae in the mutant hearts. In accordance with these changes, Popdc1-null cardiomyocytes displayed impaired [Ca(+2)](i) transients, increased vulnerability to oxidative stress and no pharmacologic preconditioning. In addition, induction of I/R injury to Langendorff-perfused hearts indicated a significantly lower functional recovery in the mutant compared with wild type hearts while their infarct size was larger. No improvement in functional recovery was observed in Popdc1-null hearts following ischemic preconditioning. The results indicate that Popdc1 is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity and for heart protection. Public Library of Science 2013-09-16 /pmc/articles/PMC3774711/ /pubmed/24066022 http://dx.doi.org/10.1371/journal.pone.0071100 Text en © 2013 Alcalay et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Alcalay, Yifat Hochhauser, Edith Kliminski, Vitaly Dick, Julia Zahalka, Muayad A. Parnes, Doris Schlesinger, Hadassa Abassi, Zaid Shainberg, Asher Schindler, Roland F. R. Brand, Thomas Kessler-Icekson, Gania Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title | Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title_full | Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title_fullStr | Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title_full_unstemmed | Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title_short | Popeye Domain Containing 1 (Popdc1/Bves) Is a Caveolae-Associated Protein Involved in Ischemia Tolerance |
title_sort | popeye domain containing 1 (popdc1/bves) is a caveolae-associated protein involved in ischemia tolerance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774711/ https://www.ncbi.nlm.nih.gov/pubmed/24066022 http://dx.doi.org/10.1371/journal.pone.0071100 |
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