Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation
Different kinds of mechanical stimuli acting on the heart lead to different myocardial phenotypes. Physiological stress, such as exercise, leads to adaptive cardiac hypertrophy, which is characterized by a normal cardiac structure and improved cardiac function. Pathological stress, such as sustained...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.678863/full |
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| author | Yinlong Zhao Yinlong Zhao Shukuan Ling Guohui Zhong Guohui Zhong Yuheng Li Jianwei Li Ruikai Du Xiaoyan Jin Dingsheng Zhao Zizhong Liu Guanghan Kan Yan-Zhong Chang Yingxian Li |
| author_facet | Yinlong Zhao Yinlong Zhao Shukuan Ling Guohui Zhong Guohui Zhong Yuheng Li Jianwei Li Ruikai Du Xiaoyan Jin Dingsheng Zhao Zizhong Liu Guanghan Kan Yan-Zhong Chang Yingxian Li |
| author_sort | Yinlong Zhao |
| collection | DOAJ |
| description | Different kinds of mechanical stimuli acting on the heart lead to different myocardial phenotypes. Physiological stress, such as exercise, leads to adaptive cardiac hypertrophy, which is characterized by a normal cardiac structure and improved cardiac function. Pathological stress, such as sustained cardiac pressure overload, causes maladaptive cardiac remodeling and, eventually, heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) is an important regulator of pathological cardiac remodeling. However, the role of CKIP-1 in physiological cardiac hypertrophy is unknown. We subjected wild-type (WT) mice to a swimming exercise program for 21 days, which caused an increase in myocardial CKIP-1 protein and mRNA expression. We then subjected CKIP-1 knockout (KO) mice and myocardial-specific CKIP-1-overexpressing mice to the 21-day swimming exercise program. Histological and echocardiography analyses revealed that CKIP-1 KO mice underwent pathological cardiac remodeling after swimming, whereas the CKIP-1-overexpressing mice had a similar cardiac phenotype to the WT controls. Histone deacetylase 4 (HDAC4) is a key molecule in the signaling cascade associated with pathological hypertrophy; the phosphorylation levels of HDAC4 were markedly higher in CKIP-1 KO mouse hearts after the swimming exercise program. The phosphorylation levels of HDAC4 did not change after swimming in the hearts of CKIP-1-overexpressing or WT mice. Our results indicate that swimming, a mechanical stress that leads to physiological hypertrophy, triggers pathological cardiac remodeling in CKIP-1 KO mice. CKIP-1 is necessary for physiological cardiac hypertrophy in vivo, and for modulating the phosphorylation level of HDAC4 after physiological stress. Genetically engineering CKIP-1 expression affected heart health in response to exercise. |
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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-17T00:17:46Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-2afc90eb2ea44bbdb54098e6b95c5bc42022-12-21T22:10:39ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.678863678863Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 PhosphorylationYinlong Zhao0Yinlong Zhao1Shukuan Ling2Guohui Zhong3Guohui Zhong4Yuheng Li5Jianwei Li6Ruikai Du7Xiaoyan Jin8Dingsheng Zhao9Zizhong Liu10Guanghan Kan11Yan-Zhong Chang12Yingxian Li13Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaSchool of Aerospace Medicine, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaKey Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaDifferent kinds of mechanical stimuli acting on the heart lead to different myocardial phenotypes. Physiological stress, such as exercise, leads to adaptive cardiac hypertrophy, which is characterized by a normal cardiac structure and improved cardiac function. Pathological stress, such as sustained cardiac pressure overload, causes maladaptive cardiac remodeling and, eventually, heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) is an important regulator of pathological cardiac remodeling. However, the role of CKIP-1 in physiological cardiac hypertrophy is unknown. We subjected wild-type (WT) mice to a swimming exercise program for 21 days, which caused an increase in myocardial CKIP-1 protein and mRNA expression. We then subjected CKIP-1 knockout (KO) mice and myocardial-specific CKIP-1-overexpressing mice to the 21-day swimming exercise program. Histological and echocardiography analyses revealed that CKIP-1 KO mice underwent pathological cardiac remodeling after swimming, whereas the CKIP-1-overexpressing mice had a similar cardiac phenotype to the WT controls. Histone deacetylase 4 (HDAC4) is a key molecule in the signaling cascade associated with pathological hypertrophy; the phosphorylation levels of HDAC4 were markedly higher in CKIP-1 KO mouse hearts after the swimming exercise program. The phosphorylation levels of HDAC4 did not change after swimming in the hearts of CKIP-1-overexpressing or WT mice. Our results indicate that swimming, a mechanical stress that leads to physiological hypertrophy, triggers pathological cardiac remodeling in CKIP-1 KO mice. CKIP-1 is necessary for physiological cardiac hypertrophy in vivo, and for modulating the phosphorylation level of HDAC4 after physiological stress. Genetically engineering CKIP-1 expression affected heart health in response to exercise.https://www.frontiersin.org/articles/10.3389/fphys.2021.678863/fullCKIP-1swimmingphysiological cardiac hypertrophypathological cardiac remodelingHDAC4 |
| spellingShingle | Yinlong Zhao Yinlong Zhao Shukuan Ling Guohui Zhong Guohui Zhong Yuheng Li Jianwei Li Ruikai Du Xiaoyan Jin Dingsheng Zhao Zizhong Liu Guanghan Kan Yan-Zhong Chang Yingxian Li Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation Frontiers in Physiology CKIP-1 swimming physiological cardiac hypertrophy pathological cardiac remodeling HDAC4 |
| title | Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation |
| title_full | Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation |
| title_fullStr | Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation |
| title_full_unstemmed | Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation |
| title_short | Casein Kinase-2 Interacting Protein-1 Regulates Physiological Cardiac Hypertrophy via Inhibition of Histone Deacetylase 4 Phosphorylation |
| title_sort | casein kinase 2 interacting protein 1 regulates physiological cardiac hypertrophy via inhibition of histone deacetylase 4 phosphorylation |
| topic | CKIP-1 swimming physiological cardiac hypertrophy pathological cardiac remodeling HDAC4 |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.678863/full |
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