Inhibitory effect of glycyrrhizin on the phosphorylation and DNA-binding abilities of high mobility group proteins 1 and 2 in vitro.
The physiological correlation between glycyrrhizin (GL) and high mobility group proteins I and 2 (HMG1/2) and the inhibitory effect of GL on their phosphorylation by three protein kinases (CK-I, CK-II and PKC) were investigated biochemically in vitro. It was found that GL binds directly to HMG1/2, because (i) HMG1/2 have a high affinity with a GL-affinity column; and (ii) GL induces the conformational changes in HMG1/2. Both purified HMG1/2 functioned as phosphate acceptors for these two protein kinases (CK-I and PKC), but not phosphorylated by CK-II. Phosphorylation of HMG1/2 by two protein kinases (CK-I and PKC) was completely inhibited by a glycyrrhetinic acid derivative (oGA) at one-tenth the concentration of GL. Also, the DNA-binding abilities of HNG1/2 were reduced by GL in a dose-dependent manner. These results show that the binding of GL to HMG1/2 results in the inhibition of their physiological activities (DNA-binding ability and phosphorylation by PKC or CK-I) in vitro. The GL-induced inhibition of the physiological activities of HMG1/2 may be involved in the anti-inflammatory effect of GL in vivo.
Sakamoto
R
R
Laboratory of Genetical Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Okano
M
M
Takena
H
H
Ohtsuki
K
K
D000818:Animals; D002849:Chromatography, Gas; D002942:Circular Dichroism; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006609:High Mobility Group Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013950:Thymus Gland / Q000737:chemistry
D006609:High Mobility Group Proteins; D019695:Glycyrrhizic Acid; D004247:DNA; D011493:Protein Kinase C; D003402:Creatine Kinase; D006034:Glycyrrhetinic Acid