These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activation of peroxisome proliferator-activated receptor-alpha decreases endothelin-1-induced p38 mitogen-activated protein kinase activation in cardiomyocytes.
    Author: Irukayama-Tomobe Y, Miyauchi T, Kasuya Y, Sakai S, Goto K, Yamaguchi I.
    Journal: J Cardiovasc Pharmacol; 2004 Nov; 44 Suppl 1():S358-61. PubMed ID: 15838320.
    Abstract:
    Endothelin-1 (ET-1) is synthesized and secreted by cardiomyocytes and induces cardiac hypertrophy. 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, such as nuclear factor-kappaB and activator protein-1 (AP-1). We reported that PPAR-alpha activator, fenofibrate (10 microM), and PPAR-alpha overexpression markedly inhibited the ET-1-induced increase in protein synthesis in cultured neonatal rat cardiomyocytes. Activation of protein kinase C and one or more of the mitogen-activated protein kinase cascades by ET-1 induces many of the features of hypertrophy. We demonstrated that PPAR-alpha activation significantly inhibits ET-1-induced cardiac hypertrophy through negative regulation of AP-1 binding activity partly secondary to inhibition of the JNK pathway. Zechner et al. demonstrated a significant role of p38 mitogen-activated protein kinase (p38) in myocardial cell hypertrophic growth and gene expression. Therefore, we investigated the effect of fenofibrate on ET-1-induced p38 activation in cardiomyocytes. The phosphorylation of p38 was transiently increased after 15 and 30 minutes of stimulation with ET-1, which was significantly inhibited by fenofibrate (10 microM). Neither application of ET-1 nor fenofibrate treatment affected the expression level of p38 in cardiomyocytes. These results suggest that the negative effect of the PPAR-alpha activator, fenofibrate, on ET-1-induced cardiac hypertrophy may be partly due to inhibition of the p38 signaling pathway.
    [Abstract] [Full Text] [Related] [New Search]