Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues
Summary: BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death mechanisms. Its dysregulation and altered ratio of splicing variants associate with pathologies. However, isoform-specific loss-of-function analysis of BCL2L1 remains unexplored. Here we show the functional impact o...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223004868 |
| _version_ | 1797857677818200064 |
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| author | Mariko Aoyagi Keller Chun-yang Huang Andreas Ivessa Sukhwinder Singh Peter J. Romanienko Michinari Nakamura |
| author_facet | Mariko Aoyagi Keller Chun-yang Huang Andreas Ivessa Sukhwinder Singh Peter J. Romanienko Michinari Nakamura |
| author_sort | Mariko Aoyagi Keller |
| collection | DOAJ |
| description | Summary: BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death mechanisms. Its dysregulation and altered ratio of splicing variants associate with pathologies. However, isoform-specific loss-of-function analysis of BCL2L1 remains unexplored. Here we show the functional impact of genetically inhibiting Bcl-x short-isoform (Bcl-xS) in vivo. Bcl-xS is expressed in most tissues with predominant expression in the spleen and blood cells in mice. Bcl-xS knockout (KO) mice show no overt abnormality until 3 months of age. Thereafter, KO mice develop cardiac hypertrophy with contractile dysfunction and splenomegaly by 6 months. Cardiac fibrosis significantly increases in KO, but the frequency of apoptosis is indistinguishable despite cardiomyopathy. The Akt/mTOR and JNK/cJun signaling are upregulated in male KO heart, and the JNK/cJun is activated with increased Bax expression in KO spleen. These results suggest that Bcl-xS may be dispensable for development but is essential for maintaining the homeostasis of multiple organs. |
| first_indexed | 2024-04-09T21:00:40Z |
| format | Article |
| id | doaj.art-4aa4f8fb0b914793b9530458ea482ea0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T21:00:40Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4aa4f8fb0b914793b9530458ea482ea02023-03-29T09:28:52ZengElsevieriScience2589-00422023-04-01264106409Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissuesMariko Aoyagi Keller0Chun-yang Huang1Andreas Ivessa2Sukhwinder Singh3Peter J. Romanienko4Michinari Nakamura5Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112, Taiwan; Institute of Clinical Medicine, School of Medicine National Yang-Ming University, Taipei, 112, TaiwanDepartment of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USAGenome Editing Shared Resource, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USADepartment of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Corresponding authorSummary: BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death mechanisms. Its dysregulation and altered ratio of splicing variants associate with pathologies. However, isoform-specific loss-of-function analysis of BCL2L1 remains unexplored. Here we show the functional impact of genetically inhibiting Bcl-x short-isoform (Bcl-xS) in vivo. Bcl-xS is expressed in most tissues with predominant expression in the spleen and blood cells in mice. Bcl-xS knockout (KO) mice show no overt abnormality until 3 months of age. Thereafter, KO mice develop cardiac hypertrophy with contractile dysfunction and splenomegaly by 6 months. Cardiac fibrosis significantly increases in KO, but the frequency of apoptosis is indistinguishable despite cardiomyopathy. The Akt/mTOR and JNK/cJun signaling are upregulated in male KO heart, and the JNK/cJun is activated with increased Bax expression in KO spleen. These results suggest that Bcl-xS may be dispensable for development but is essential for maintaining the homeostasis of multiple organs.http://www.sciencedirect.com/science/article/pii/S2589004223004868Cardiovascular medicineCell biologyDevelopmental biology |
| spellingShingle | Mariko Aoyagi Keller Chun-yang Huang Andreas Ivessa Sukhwinder Singh Peter J. Romanienko Michinari Nakamura Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues iScience Cardiovascular medicine Cell biology Developmental biology |
| title | Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues |
| title_full | Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues |
| title_fullStr | Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues |
| title_full_unstemmed | Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues |
| title_short | Bcl-x short-isoform is essential for maintaining homeostasis of multiple tissues |
| title_sort | bcl x short isoform is essential for maintaining homeostasis of multiple tissues |
| topic | Cardiovascular medicine Cell biology Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223004868 |
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