Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis. Aldosterone (1 microM) induced apoptosis by increasing terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei in ARVM. Spironolactone (100 nM), an aldosterone receptor antagonist, but not RU-486, a glucocorticoid receptor, inhibited aldosterone-mediated apoptosis, indicating that the mineralocorticoid receptor (MR) plays a role. SP-600125 (3 microM)-a selective inhibitor of c-Jun NH(2)-terminal kinase (JNK)-inhibited aldosterone-induced apoptosis in ARVM. Although aldosterone increased the expression of both stress-activated protein kinases, pretreatment with fenofibrate (10 microM) decreased aldosterone-mediated apoptosis by inhibiting only JNK phosphorylation and the aldosterone-induced increases in Bax, p53, and cleaved caspase-3 and decreases in Bcl-2 protein expression in ARVM. In vivo studies demonstrated that chronic fenofibrate (100 mg*kg body wt(-1)*day(-1)) inhibited myocardial Bax and increased Bcl-2 expression in aldosterone-induced cardiac hypertrophy. Similarly, eplerenone, a selective MR inhibitor, used in chronic pressure-overload ascending aortic constriction inhibited myocardial Bax expression but had no effect on Bcl-2 expression. Therefore, involvement of JNK MAPK-dependent mitochondrial death pathway mediates ARVM aldosterone-induced apoptosis and is inhibited by fenofibrate, a peroxisome proliferator-activated receptor (PPAR)alpha ligand. Fenofibrate mediates beneficial effects in cardiac remodeling by inhibiting programmed cell death and the stress-activated kinases.
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PMID:Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms. 1939 58

Fenofibrate is a lipid-lowering agent and supposed to have anti-inflammatory properties. But it was rarely evaluated for the signal transduction on human primary T cells. Therefore, the methods including enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility shift assay, luciferase assay and Western blotting were used to investigate the mechanisms of fenofibrate on human primary T cells, isolated from normal human beings. We found that fenofibrate could dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, tumor necrosis factor-alpha and interferon-gamma from activated T cells. Also, it could down-regulate activator protein-1 (AP-1) DNA-binding activities in T cells. As performing in vivo study, fenofibrate reduced the AP-1 transcriptional activity in Jurkat cells. Finally, fenofibrate inhibited the activation of c-Jun NH2-terminal protein kinase and P38 mitogen-activated protein kinase. These results may extend potential therapeutic mechanisms of fenofibrate on cardiovascular disease with inflammatory processes.
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PMID:The modulatory mechanisms of fenofibrate on human primary T cells. 2041 10