Activation of peroxisome proliferator-activated receptor-α prevents glycogen synthase 3β phosphorylation and inhibits cardiac hypertrophy

Autor: Wenhua Zheng, Ruifang Li, Kang Le, Huijie Zhang, Peiqing Liu, Rongbiao Pi, Jie Gao, Ping Wang
Rok vydání: 2007
Předmět:
medicine.medical_specialty
Biophysics
Peroxisome proliferator-activated receptor
Cardiomegaly
Nerve Tissue Proteins
Transfection
Biochemistry
Rats
Sprague-Dawley
Glycogen Synthase Kinase 3
Fenofibrate
Structural Biology
Internal medicine
Genetics
medicine
Animals
Myocytes
Cardiac
PPAR alpha
Phosphorylation
Receptor
Glycogen synthase
Peroxisome proliferator-activated receptor-α
Molecular Biology
Protein kinase B
Cells
Cultured
PI3K/AKT/mTOR pathway
Cell Nucleus
chemistry.chemical_classification
Glycogen Synthase Kinase 3 beta
Endothelin-1
NFATC Transcription Factors
biology
NFAT
Cell Biology
Rats
Nuclear factor of activated T cells
Protein Transport
Cardiac hypertrophy
Glycogen synthase kinase
Endocrinology
Animals
Newborn
Gene Expression Regulation
chemistry
biology.protein
Signal transduction
Zdroj: FEBS Letters. 581:3311-3316
ISSN: 0014-5793
Popis: Activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) has been recently reported to inhibit vascular inflammatory response and prevent cardiac hypertrophy. However, it is unclear how the activation of PPAR-alpha regulates hypertrophic response. In the present study, we found that application of fenofibrate and overexpression of PPAR-alpha inhibited endothelin-1 (ET-1)-induced phosphorylation of protein kinase B (Akt) at Ser473 and glycogen synthase kinase3beta (GSK3beta) at Ser9, and prevented ET-1-induced nuclear translocation of NFATc4 in cardiomyocytes. Moreover, co-immunoprecipitation studies showed that fenofibrate strongly induced the association of nuclear factor of activated T cells (NFATc4) with PPAR-alpha. These results suggest that activation of PPAR-alpha inhibits ET-1-induced cardiac hypertrophy through regulating PI3K/Akt/GSK3beta and NFAT signaling pathways.
Databáze: OpenAIRE
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