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

被引：0
作者：
Wei-Wen Kuo
Chung-Jung Liu
Li-Ming Chen
Chieh-Hsi Wu
Chun-Hsien Chu
Jer-Yuh Liu
Min-Chi Lu
James A. Lin
Shin-Da Lee
Chih-Yang Huang
机构：
[1] China Medical University,Department of Biological Science and Technology
[2] Chung-Shan Medical University,Institute of Biochemistry and Biotechnology
[3] China Medical University,Graduate Institute of Chinese Medical Science, School of Chinese Medicine
[4] Armed Forces Taichung General Hospital,Department of Internal Medicine
[5] Chung-Shan Medical University,Department of Internal Medicine and Microbiology and Immunology
[6] National Chung-Hsing University,Department of Veterinary Medicine
[7] Chung-Shan Medical University,Department of Physical Therapy
来源：
Apoptosis | 2006年 / 11卷
关键词：
IGF-I resistance; Angiotensin II; Calcineurin; IGF-II; Cardiomyoblast apoptosis;
D O I：
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学科分类号：
摘要：
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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页码：1075 / 1089
页数：14
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