Characterization of Secretory Type IIA Phospholipase A₂ (sPLA₂-IIA) as a Glycyrrhizin (GL)-Binding Protein and the GL-Induced Inhibition of the CK-II-Mediated Stimulation of sPLA₂-IIA Activity in Vitro

抄録

By means of heparin-affinity and glycyrrhizin (GL)-affinity column chromatographies (HPLC), a GL-binding phospholipase A₂ (gbPLA₂) was selectively purified from the synovial fluids of patients with rheumatoid arthritis. This purified gbPLA₂ was identified as a secretory type IIA PLA₂ (sPLA₂-IIA) since it was crossreacted with anti-sPLA₂-IIA serum. The activity of purified sPLA₂-IIA was inhibited by glycyrrhetinic acid (GA) and a GA derivative (oGA) in a dose-dependent manner, but it was more sensitive to GA than GL. Furthermore, it was found that (i) purified sPLA₂-IIA is phosphorylated by casein kinase II (CK-II) in vitro; (ii) this phosphorylation induces in a significant stimulation of PLA₂ activity; and (iii) oGA at one-tenth the concentration of GL inhibits the CK-II-mediated stimulation of sPLA₂-IIA activity. These results show that (i) sPLA₂-IIA is a GL-binding protein; and (ii) CK-II mediates stimulation of its PLA₂ activity in vitro.