Search

Your search keyword '"Miyauchi, Takashi"' showing total 10 results
Start Over Author "Miyauchi, Takashi" Journal circulation
10 results on '"Miyauchi, Takashi"'

3. Endothelin-1–Induced Cardiac Hypertrophy Is Inhibited by Activation of Peroxisome Proliferator–Activated Receptor-α Partly Via Blockade of c-Jun NH 2 -Terminal Kinase Pathway

Author

Irukayama-Tomobe, Yoko, primary, Miyauchi, Takashi, additional, Sakai, Satoshi, additional, Kasuya, Yoshitoshi, additional, Ogata, Takehiro, additional, Takanashi, Masakatsu, additional, Iemitsu, Motoyuki, additional, Sudo, Tatsuhiko, additional, Goto, Katsutoshi, additional, and Yamaguchi, Iwao, additional

Published
2004
Full Text
View/download PDF

10. Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-alpha partly via blockade of c-Jun NH2-terminal kinase pathway.

Author

Irukayama-Tomobe Y, Miyauchi T, Sakai S, Kasuya Y, Ogata T, Takanashi M, Iemitsu M, Sudo T, Goto K, and Yamaguchi I

Subjects
Animals, Animals, Newborn, Aorta, Cells, Cultured drug effects, Cells, Cultured enzymology, Disease Models, Animal, Endothelin-1 biosynthesis, Endothelin-1 genetics, Genes, fos, Genes, jun drug effects, Hypertrophy, Left Ventricular chemically induced, Hypertrophy, Left Ventricular drug therapy, Hypertrophy, Left Ventricular metabolism, JNK Mitogen-Activated Protein Kinases, Ligation, MAP Kinase Signaling System drug effects, Mitogen-Activated Protein Kinases physiology, Myocytes, Cardiac enzymology, Phosphorylation drug effects, Protein Processing, Post-Translational drug effects, Proto-Oncogene Proteins c-fos biosynthesis, Proto-Oncogene Proteins c-jun biosynthesis, Proto-Oncogene Proteins c-jun physiology, RNA, Messenger biosynthesis, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear agonists, Receptors, Cytoplasmic and Nuclear biosynthesis, Receptors, Cytoplasmic and Nuclear genetics, Tetradecanoylphorbol Acetate pharmacology, Transcription Factor AP-1 antagonists & inhibitors, Transcription Factor AP-1 metabolism, Transcription Factors agonists, Transcription Factors biosynthesis, Transcription Factors genetics, Endothelin-1 toxicity, Fenofibrate pharmacology, Hypertrophy, Left Ventricular prevention & control, Mitogen-Activated Protein Kinases antagonists & inhibitors, Myocytes, Cardiac drug effects, Receptors, Cytoplasmic and Nuclear physiology, Signal Transduction drug effects, Transcription Factors physiology
Abstract

Background: Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a lipid-activated nuclear receptor that negatively regulates the vascular inflammatory gene response by interacting with transcription factors, nuclear factor-kappaB, and AP-1. However, the roles of PPAR-alpha activators in endothelin (ET)-1-induced cardiac hypertrophy are not yet known., Methods and Results: First, in cultured neonatal rat cardiomyocytes, a PPAR-alpha activator, fenofibrate (10 micromol/L), and PPAR-alpha overexpression markedly inhibited the ET-1-induced increase in protein synthesis. Second, fenofibrate markedly inhibited ET-1-induced increase in c-Jun gene expression and phosphorylation of c-Jun and JNK. These results suggest that this PPAR-alpha activator interferes with the formation and activation of AP-1 protein induced by ET-1 in cardiomyocytes. Third, fenofibrate significantly inhibited the increase of ET-1 mRNA level by ET-1, which was also confirmed by luciferase assay. Electrophoretic mobility shift assay revealed that fenofibrate significantly decreased the ET-1-stimulated or phorbol 12-myristate 13-acetate-stimulated AP-1 DNA binding activity, and the nuclear extract probe complex was supershifted by anti-c-Jun antibody. Fourth, 24 hours after aortic banding (AB) operation, fenofibrate treatment significantly inhibited left ventricular hypertrophy and hypertrophy-related gene expression pattern (ET-1, brain natriuretic peptide, and beta-myosin heavy chain mRNA) in AB rats., Conclusions: These results suggest that PPAR-alpha activation interferes with the signaling pathway of ET-1-induced cardiac hypertrophy through negative regulation of AP-1 binding activity, partly via inhibition of the JNK pathway in cultured cardiomyocytes. We also revealed that fenofibrate treatment inhibited left ventricle hypertrophy and phenotypic changes in cardiac gene expression in AB rats in vivo.

Published
2004
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results