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BNIP3 induces IL6 and calcineurin/NFAT3 hypertrophic-related pathways in H9c2 cardiomyoblast cells

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Abstract

Ischemia/reperfusion injury causes cardiomyocyte apoptosis, ventricular remodeling, leading to a dilated heart. Hypoxia is one of the causes involved in ischemia damage, and BNIP3 is a hypoxia-inducible marker and also a sensor to induce mitochondria-dependent apoptosis. Recent reports discussed ablating BNIP3 can restrain cardiomyocytes apoptosis and post-infarction remodeling. BNIP3 is a crucial therapeutic target. However, the BNIP3-induced hypertrophy aspect is rarely investigated. Here, we transiently transfected BNIP3 plasmids into H9c2 cardiomyoblast cells to evaluate the molecular signaling and hypertrophy markers using Western blot. We measured the cell size change using actin staining. We disclose that BNIP3 overexpression induced an increase in cell size, activated the pathological-related hypertrophy signaling pathways, such as IL6-MEK5-ERK5, IL6-JAK2-STAT1/3, calcineurin/NFAT3 and p38β MAPK resulting in the fetal genes, ANP and BNP expressing. Concluding above, BNIP3 acts as a pathological hypertrophy inducer, which might be a potential therapeutic target for heart damage prevention.

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Abbreviations

ANP:

Atrial natriuretic peptide

BNP:

B-type natriuretic peptide

ERK5:

Extracellular-regulated kinase 5

IL6:

Interleukin-6

JAK2:

Janus kinase 2

β-MHC:

β-Myosin heavy chain

MAPK:

Mitogen-activated protein kinase

NFAT3:

Nuclear factor of activated T cells 3

STAT1/3:

Signal transducers and activators of transcription-1,-3

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Acknowledgments

This study is supported by Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH99-TD-B-111-004) and in part by Taiwan Department of Health Cancer Research Center of Excellence (DOH99-TD-C-111-005).

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Authors and Affiliations

  1. Department of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan, ROC

    Yi-Jiun Weng & Kwong-Chung Tung

  2. Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, ROC

    Wei-Wen Kuo

  3. Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 105, Taiwan, ROC

    Chia-Hua Kuo

  4. Department of Healthcare Administration, Asia University, Taichung, Taiwan, ROC

    Chang-Hai Tsai

  5. Graduate Institute of Basic Medical Science, Taichung, Taiwan, ROC

    James A. Lin & Chih-Yang Huang

  6. Department of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC

    Fuu-Jen Tsai & Chih-Yang Huang

  7. School of Medical Technology, Chung Shan Medical University, Taichung 402, Taiwan, ROC

    Dennis Jine-Yuan Hsieh

  8. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC

    Chih-Yang Huang

  9. School of Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung 402, Taiwan, ROC

    Jin-Ming Hwang

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  1. Yi-Jiun Weng
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  2. Wei-Wen Kuo
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  7. Fuu-Jen Tsai
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  10. Jin-Ming Hwang
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Correspondence to Jin-Ming Hwang.

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Dennis Jine-Yuan Hsieh, Chih-Yang Huang, and Jin-Ming Hwang share equal contribution.

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Weng, YJ., Kuo, WW., Kuo, CH. et al. BNIP3 induces IL6 and calcineurin/NFAT3 hypertrophic-related pathways in H9c2 cardiomyoblast cells. Mol Cell Biochem 345, 241–247 (2010). https://doi.org/10.1007/s11010-010-0578-3

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  • DOI: https://doi.org/10.1007/s11010-010-0578-3

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