Ursodeoxycholic acid-dependent activation of the glucocorticoid receptor.
Therapeutic effectiveness of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis strongly indicates that UDCA possesses immunomodulatory activities. In order to further investigate mechanical background of such UDCA action, we first asked whether UDCA modulates glucocorticoid-mediated signal transduction. Using electrophoretic mobility-shift assay, we demonstrated that treatment with UDCA promoted the specific complex formation between the cytosol protein and the glucocorticoid-response element DNA in a dose-dependent fashion in vitro, and also nuclear translocation of the glucocorticoid receptor (GR) in vivo. Gene transfer experiments revealed that UDCA induced cellular CAT activities in a GR-dependent fashion, but rather weakly as compared to synthetic glucocorticoid dexamethasone.
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
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Tanaka
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Makino
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014444:Tyrosine Transaminase / Q000235:genetics / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D015345:Oligonucleotide Probes; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D014580:Ursodeoxycholic Acid; D015500:Chloramphenicol O-Acetyltransferase; D014444:Tyrosine Transaminase