Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes
Isolated adult rat ventricular cardiomyocytes (ARVC) adapt to the two-dimensional surface of culture dishes once they are isolated from the three-dimensional heart tissue. This process mimics aspects of cardiac adaptation to pressure overload and requires an initial breakdown of sarcomeric structure...
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MDPI AG
2020-05-01
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| Series: | Medical Sciences |
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| Online Access: | https://www.mdpi.com/2076-3271/8/2/21 |
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| author | Antonia Petersen Hanna Sarah Kutsche Franziska Nippert Rolf Schreckenberg Rainer Schulz Klaus-Dieter Schlüter |
| author_facet | Antonia Petersen Hanna Sarah Kutsche Franziska Nippert Rolf Schreckenberg Rainer Schulz Klaus-Dieter Schlüter |
| author_sort | Antonia Petersen |
| collection | DOAJ |
| description | Isolated adult rat ventricular cardiomyocytes (ARVC) adapt to the two-dimensional surface of culture dishes once they are isolated from the three-dimensional heart tissue. This process mimics aspects of cardiac adaptation to pressure overload and requires an initial breakdown of sarcomeric structures. The present study therefore aimed to identify key steps in this remodeling process. ARVC were cultured under serum-free or serum-supplemented conditions and their sizes and shapes were analyzed as well as apoptosis and the ability to disintegrate their sarcomeres. ARVC require serum-factors in order to adapt to cell culture conditions. More ARVC survived if they were able to breakdown their sarcomeres and mononucleated ARVC, which were smaller than binucleated ARVC, had a better chance to adapt. During the early phase of adaptation, proteasome subunit low molecular weight protein (LMP)-2 was induced. Inhibition of LMP-2 up-regulation by siRNA attenuated the process of successful adaptation. In vivo, LMP-2 was induced in the left ventricle of spontaneously hypertensive rats during the early phase of adaptation to pressure overload. In conclusion, the data suggest that breakdown of pre-existing sarcomeres is optimized by induction of LMP-2 and that it is required for cardiac remodeling processes, for example, occurring during pressure overload. |
| first_indexed | 2024-03-10T20:05:38Z |
| format | Article |
| id | doaj.art-905d4e4b19c34d40bad8532b28bafe1e |
| institution | Directory Open Access Journal |
| issn | 2076-3271 |
| language | English |
| last_indexed | 2024-03-10T20:05:38Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medical Sciences |
| spelling | doaj.art-905d4e4b19c34d40bad8532b28bafe1e2023-11-19T23:16:45ZengMDPI AGMedical Sciences2076-32712020-05-01822110.3390/medsci8020021Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular CardiomyocytesAntonia Petersen0Hanna Sarah Kutsche1Franziska Nippert2Rolf Schreckenberg3Rainer Schulz4Klaus-Dieter Schlüter5Department of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyDepartment of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyDepartment of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyDepartment of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyDepartment of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyDepartment of Physiology, Justus-Liebig-University, 35392 Giessen, GermanyIsolated adult rat ventricular cardiomyocytes (ARVC) adapt to the two-dimensional surface of culture dishes once they are isolated from the three-dimensional heart tissue. This process mimics aspects of cardiac adaptation to pressure overload and requires an initial breakdown of sarcomeric structures. The present study therefore aimed to identify key steps in this remodeling process. ARVC were cultured under serum-free or serum-supplemented conditions and their sizes and shapes were analyzed as well as apoptosis and the ability to disintegrate their sarcomeres. ARVC require serum-factors in order to adapt to cell culture conditions. More ARVC survived if they were able to breakdown their sarcomeres and mononucleated ARVC, which were smaller than binucleated ARVC, had a better chance to adapt. During the early phase of adaptation, proteasome subunit low molecular weight protein (LMP)-2 was induced. Inhibition of LMP-2 up-regulation by siRNA attenuated the process of successful adaptation. In vivo, LMP-2 was induced in the left ventricle of spontaneously hypertensive rats during the early phase of adaptation to pressure overload. In conclusion, the data suggest that breakdown of pre-existing sarcomeres is optimized by induction of LMP-2 and that it is required for cardiac remodeling processes, for example, occurring during pressure overload.https://www.mdpi.com/2076-3271/8/2/21cardiac remodelingcardiac hypertrophyproteasome |
| spellingShingle | Antonia Petersen Hanna Sarah Kutsche Franziska Nippert Rolf Schreckenberg Rainer Schulz Klaus-Dieter Schlüter Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes Medical Sciences cardiac remodeling cardiac hypertrophy proteasome |
| title | Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes |
| title_full | Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes |
| title_fullStr | Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes |
| title_full_unstemmed | Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes |
| title_short | Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes |
| title_sort | induction of proteasome subunit low molecular weight protein lmp 2 is required to induce active remodeling in adult rat ventricular cardiomyocytes |
| topic | cardiac remodeling cardiac hypertrophy proteasome |
| url | https://www.mdpi.com/2076-3271/8/2/21 |
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