Long-term hypoxia exposure enhanced IGFBP-3 protein synthesis and secretion resulting in cell apoptosis in H9c2 myocardial cells.
Myocardial infarction (MI) usually results in myocardial ischemia, remodeling and hypoxia that lead to cell death. To date, the insulin-like growth factor binding protein-3 (IGFBP3) is known to play an important role in insulin growth factor (IGF) bioavailability. Previous studies have found that hypoxia results in cell apoptosis. However, the detailed mechanism and roles of IGFBP3 in long-term hypoxia (LTH) regulated heart cell apoptosis remains unknown. In this study H9c2 cardiomyoblast cells were treated with investigated long-term hypoxic exposure with the possible mechanisms involved. The results showed that LTH enhanced IGFBP3 protein synthesis and induced its secretion. The accumulated IGFBP3 sequestered Insulin growth factor 1 (IGF-1) away from the type I IGF receptor (IGF-1 R), which blocked the IGF1R/PI3K/Akt survival signaling pathway, resulting in cell apoptosis. According to our findings, IGFBP3 could be a valuable target for developing treatments for cardiac diseases in long-term hypoxia exposure patients.
a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .
Ruey-Lin
RL
Chang
a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .
Jing-Wei
JW
Lin
b School of Medical Laboratory and Biotechnology, Chung Shan Medical University , Taichung , Taiwan .
Dennis Jine-Yuan
DJ
Hsieh
c Department of Pathology , Changhua Christian Hospital , Changhua , Taiwan .|d en-Teh Junior College of Medicine, Nursing and Management , Miaoli , Taiwan .
Yu-Lan
YL
Yeh
e Department of Nursing , Mei Ho University , Pingtung , Taiwan .
Chia-Yao
CY
Shen
e Department of Nursing , Mei Ho University , Pingtung , Taiwan .
Cecilia-Hsuan
CH
Day
f Chinese Medicine Department , China Medical University Beigang Hospital , Taichung , Taiwan .
Tsung-Jung
TJ
Ho
g Department of Biotechnology , Bharathiar University , Coimbatore , Tamil Nadu , India .
Vijaya Padma
VP
Viswanadha
h Department of Biological Science and Technology , China Medical University , Taichung , Taiwan .
Wei-Wen
WW
Kuo
a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .|i Graduate Institute of Chinese Medical Science, China Medical University , Taichung , Taiwan , and.|j Department of Health and Nutrition Biotechnology , Asia University , Taichung , Taiwan.
Chih-Yang
CY
Huang
D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D005089:Exocytosis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D010100:Oxygen
H9c2 cells; IGFBP3; long-term hypoxia; myocardial apoptosis