Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.
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- HAMANO Takako
- Toxicology Laboratory, Mitsubishi Pharma Co. Graduate School of Humanities and Sciences, Ochanomizu University
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- KOBAYASHI Kiyoshi
- Toxicology Laboratory, Mitsubishi Pharma Co.
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- SAKAIRI Tetsuya
- Toxicology Laboratory, Mitsubishi Pharma Co.
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- HAYASHI Masao
- Graduate School of Humanities and Sciences, Ochanomizu University
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- MUTAI Mamoru
- Toxicology Laboratory, Mitsubishi Pharma Co.
Bibliographic Information
- Other Title
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- Peroxisome proliferator-activated receptor α(PPARα)agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes
- Peroxisome proliferator activated receptor アルファ PPAR アルファ agonist WY 14 643 increased transcription of myosin light chain 2 in cardiomyocytes
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Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that can be activated by xenobiotics and natural fatty acids. To assess the potential physiological activity of PPAR ligands on cardiac muscular cells, the effects of PPARα agonist, WY-14,643, on both rat hearts and a rat cardiomyocyte cell line (H9c2 cells) were investigated. Male F344 rats were fed a diet containing WY-14,643 at a concentration of 100 ppm for 26 weeks. Cardiac muscular hypertrophy was revealed by morphometric analysis in which the diameter of the muscular fibers in WY-14,643-treated rats was larger than those of control rats. Using H9c2 cells in vitro, the protein content per cell was increased in a dose-dependent manner with the treatment of WY-14,643. The transcription of myosin light chain-2(MLC-2), a parameter of myocardial hypertrophy, was increased in H9c2 cells transfected with the rat MLC-2/luciferase fusion gene by WY-14,643 as well as other peroxisome proliferators, clofibrate and di(2-ethylhexyl) phthalate. In addition, accumulation of myosin light chain protein was confirmed in H9c2 cells treated with WY-14,643 at 10 μg/ml for 7 days or more by immunohistochemistry. These results suggest that PPARα ligands have a potential to regulate MLC-2, which is a contractile protein in cardiomyocytes and may play a part of role in the pathogenesis of cardiac hypertrophy.
Journal
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 26 (5), 275-284, 2001
The Japanese Society of Toxicology
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Details 詳細情報について
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- CRID
- 1390282679879219712
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- NII Article ID
- 110001807057
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- NII Book ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- HANDLE
- 10083/1858
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- NDL BIB ID
- 6026864
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- PubMed
- 11871124
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- Text Lang
- en
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- Data Source
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- JaLC
- IRDB
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed