BNIP3 induces IL6 and calcineurin/NFAT3 hypertrophic-related pathways in H9c2 cardiomyoblast cells.
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.
Weng
Yi-Jiun
YJ
Department of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan, ROC.
Kuo
Wei-Wen
WW
Kuo
Chia-Hua
CH
Tung
Kwong-Chung
KC
Tsai
Chang-Hai
CH
Lin
James A
JA
Tsai
Fuu-Jen
FJ
Hsieh
Dennis Jine-Yuan
DJ
Huang
Chih-Yang
CY
Hwang
Jin-Ming
JM
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D049108:Cell Enlargement / Q000187:drug effects; D048429:Cell Size; D015850:Interleukin-6 / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D024101:Mitochondrial Proteins; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C505650:BNIP3 protein, rat; D015850:Interleukin-6; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050778:NFATC Transcription Factors; D011518:Proto-Oncogene Proteins; D048051:p38 Mitogen-Activated Protein Kinases