肝細胞におけるステロイド結合Glutathione S-transferase Isozymeの同定

The glutathione S-transferases (GSTs) are known to bind bilirubin, heme, bile acids, fatty acids, and other metabolites, and recently, evidence has been presented for binding of steroid hormones to GST 1-1 (Ligandin) (Litwack, G. et al.: Nature 234, 466, 1971) and to an anionic GST (Maruyama and Listowsky,: J. Biol. Chem. 259, 12447-12455, 1984). To determine which GST isozymes can function as a high affinity steroid binding protein in the rat liver, GSTs were purified by chromatofocusing columns combined with Lysyl-GSH affinity chromatography. Binding of steroid hormones to GST isozymes was analysed by circular dichroism spectroscopy and affinity labeling with dexamethasone 21-methanesulfonate. Dexamethasone mesylate affinity labeling of cytosolic extracts indicated preferential labeling of classμ subunits of GSTs. In mixtures of the multiple rat liver GSTs, corticosterone also preferentially interacted with GST classμ, especially GST4-4, rather than other GST isozymes. Glucocorticoids such as corticosterone and dexamethasone had higher affinities than aldosterone and testosterone for binding to GST4-4. These results suggest that the binding of steroid hormones to GST classμ may be correlated with structural features and stereochemistry of the ligands. In view of the selective high-affinity binding of steroid hormones to GST4-4, this protein has the potential to function in transport, metabolism and perhaps even in the action of steroid hormones