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Cardiomyoblast apoptosis induced by insulin-like growth factor (IGF)-I resistance is IGF-II dependent and synergistically enhanced by angiotensin II

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Abstract

Objective: This study explores the synergistic effect of cardiomyoblast apoptosis induced by angiotensin II (Ang II) and Insulin-like growth factor (IGF)-I resistance, and elucidates the role of IGF-II via IGF-II receptor (R) and calcineurin pathways in apoptosis induced by Ang II and IGF-I resistance. Methods: Apoptosis of cultured cardiomyoblast H9c2 cells was assessed by DNA fragmentation on agarose gel electrophoresis, nuclear condensation stained with DAPI, and Western blot analysis of pro-apoptotic Bad and cytochrome c in various combinations of control, Ang II, antisense IGF (I or II), IGF (I or II) antibody, IGF (I or II) receptor (R) antibody, or calcineurin inhibitor (Cyclosporine A, (CsA)). Results: We found the following: (1) The combination of Ang II and IGF-I deficiencies had a synergistic effect on apoptosis, confirmed by DNA fragmentation, nuclei condensation, and increases in such pro-apoptotic proteins as Bad, cytochrome c, caspase 9, and caspase 3 in H9c2 cells. (2) IGF-II and IGF-IIR protein products were increased by antisense IGF-I and IGF-I resistance, but these IGF-II protein products were not affected by sense IGF-I and non-specific antibody IgG in H9c2 cells. (3) The alteration of Bad protein level and the release of cytochrome c, both induced by treatments containing combinations of Ang II and antisense IGF-I, IGF-I antibody or IGF-IR antibody, were inhibited by IGF-II antibody. (4) DNA fragmentation, Bad, and cytochrome c which was induced by treatments combining IGF-IR antibody with Ang II or combining IGF-IR antibody with IGF-II were remarkably attenuated by CsA. Conclusion: IGF-I deficiency and/or IGF-IR resistance induced apoptosis in cardiomyoblast cells. The apoptosis, which might have been caused by the upregulation of IGF-II and IGF-IIR genes possibly activated the downstream calcineurin pathway, was synergistically augmented by Ang II.

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Authors and Affiliations

  1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo & Chieh-Hsi Wu

  2. Institute of Biochemistry and Biotechnology, Chung-Shan Medical University, Chien Kuo N. Rd., Taichung, 40203, Taiwan, R.O.C.

    Chung-Jung Liu, Chun-Hsien Chu & Jer-Yuh Liu

  3. Graduate Institute of Chinese Medical Science, School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 404, Taiwan

    Chih-Yang Huang

  4. Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan

    Li-Ming Chen

  5. Department of Internal Medicine and Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan

    Min-Chi Lu

  6. Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan

    James A. Lin

  7. Department of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan

    Shin-Da Lee

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  1. Wei-Wen Kuo
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  2. Chung-Jung Liu
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  3. Li-Ming Chen
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  4. Chieh-Hsi Wu
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  6. Jer-Yuh Liu
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  7. Min-Chi Lu
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  8. James A. Lin
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  9. Shin-Da Lee
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  10. Chih-Yang Huang
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Correspondence to Chih-Yang Huang.

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The last two authors contributed equally.

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Kuo, WW., Liu, CJ., Chen, LM. et al. Cardiomyoblast apoptosis induced by insulin-like growth factor (IGF)-I resistance is IGF-II dependent and synergistically enhanced by angiotensin II. Apoptosis 11, 1075–1089 (2006). https://doi.org/10.1007/s10495-006-7028-4

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  • DOI: https://doi.org/10.1007/s10495-006-7028-4

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