Ursodeoxycholic acid enhances glucocorticoid-induced tyrosine aminotransferase-gene expression in cultured rat hepatocytes.
Ursodeoxycholic acid (UDCA) is an effective treatment for immune-mediated liver diseases, suggesting that UDCA is functionally similar to glucocorticoids (GCs). We investigated the effects of UDCA on the enzyme activity and the mRNA levels of tyrosine aminotransferase (TAT), a hepatocyte-specific marker of GC action, in primary cultured rat hepatocytes. Addition of UDCA resulted in a significant increase in TAT activity in the presence of dexamethasone (DEX), compared with DEX alone, and this increase was completely suppressed by sphingosine, a protein kinase C (PKC) inhibitor, or actinomycin D, a transcriptional inhibitor. UDCA could not induce TAT activity in the absence of DEX. UDCA increased the TAT mRNA levels in the presence of DEX. In conclusion, UDCA enhances the GC-induced TAT-gene expression in hepatocytes, and UDCA-activated PKC may play a role in this upregulation.
Mitsuyoshi
H
H
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Nakashima
T
T
Inaba
K
K
Ishikawa
H
H
Nakajima
Y
Y
Sakamoto
Y
Y
Matsumoto
M
M
Okanoue
T
T
Kashima
K
K
D000818:Animals; D015415:Biomarkers; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007476:Ionophores / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D007476:Ionophores; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; D000001:Calcimycin; D014580:Ursodeoxycholic Acid; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate