Effects of glycyrrhizin on glucocorticoid signaling pathway in hepatocytes.
The cytoprotective effects of glycyrrhizin (GL) are similar to glucocorticoids. We investigated the effects of GL on the glucocorticoid receptor (GR) and on the enzyme activity of tyrosine aminotransferase (TAT), an hepatocyte-specific marker of glucocorticoid action, in rat hepatocytes. Pretreatment with GL significantly decreased the affinity of GRs for dexamethasone (DEX) and increased the period of time required for TAT activity to reach a peak after the addition of DEX. GL did not affect the amount of GR, but significantly decreased the amount of heat-shock protein 90 (HSP90) and HSP90-associated GR. Alternatively, TAT activity and TAT mRNA levels increased significantly after the addition of GL to hepatocytes pretreated with DEX. In conclusion, GL reduces the affinity of GRs for ligands through the decreased HSP90 expression, but significantly enhances the glucocorticoid-induced TAT-gene expression at the transcriptional level in rat hepatocytes.
Yoh
Takaharu
T
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Nakashima
Toshiaki
T
Sumida
Yoshio
Y
Kakisaka
Yuko
Y
Nakajima
Yoshiki
Y
Ishikawa
Hiroki
H
Sakamoto
Yoshikuni
Y
Okanoue
Takeshi
T
Mitsuyoshi
Hironori
H
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014444:Tyrosine Transaminase / Q000235:genetics / Q000378:metabolism
D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D014444:Tyrosine Transaminase