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Antithetical Regulation of α-Myosin Heavy Chain Between Fetal and Adult Heart Failure Though Shuttling of HDAC5 Regulating YY-1 Function

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Abstract

Molecular switches of myosin isoforms are known to occur in various conditions. Here, we demonstrated the result from fetal heart failure and its potential mechanisms. Fetal and adult heart failure rat models were induced by injections of isoproterenol as previously described, and Go6976 was given to heart failing fetuses. Real-time PCR and Western blot were adopted to measure the expressions of α-MHC, β-MHC and YY-1. Co-immunoprecipitation was performed to analysis whether YY-1 interacts with HDAC5. Besides, histological immunofluorescence assessment was carried out to identify the location of HDAC5. α-MHC was recorded elevated in fetal heart failure which was decreased in adult heart failure. Besides, YY-1 was observed elevated both in fetal and adult failing hearts, but YY-1 could co-immunoprecipitation with HDAC5 only in adult hearts. Nuclear localization of HDAC5 was identified in adult cardiomyocytes, while cytoplasmic localization was identified in fetuses. After Go6976 supplied, HDAC5 shuttled into nucleuses interacted with YY-1. The myosin molecular switches were reversed with worsening cardiac functions and higher mortalities. Regulation of MHC in fetal heart failure was different from adult which provided a better compensation with increased α-MHC. This kind of transition was involved with shuttling of HDAC5 regulating YY-1 function.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81070136 and 81270226).

Conflict of interest

The authors report no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China

    Jie Fang

  2. Ministry of Education Key Laboratory of Women and Children’s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

    Yifei Li, Kaiyu Zhou, Yimin Hua, Chuan Wang & Dezhi Mu

  3. Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

    Yifei Li, Kaiyu Zhou, Yimin Hua, Chuan Wang & Dezhi Mu

  4. Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, 610041, China

    Kaiyu Zhou

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  1. Jie Fang
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Correspondence to Kaiyu Zhou.

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Jie Fang and Yifei Li have contributed equally to this work.

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Fang, J., Li, Y., Zhou, K. et al. Antithetical Regulation of α-Myosin Heavy Chain Between Fetal and Adult Heart Failure Though Shuttling of HDAC5 Regulating YY-1 Function. Cardiovasc Toxicol 15, 147–156 (2015). https://doi.org/10.1007/s12012-014-9277-8

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  • DOI: https://doi.org/10.1007/s12012-014-9277-8

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