A Novel Type of Membrane-Associated Prostaglandin E Synthase

Abstract

Prostaglandin (PG) E₂ is widely distributed in various organs, and exhibits various biologically important activities such as smooth muscle dilatation/contraction, body temperature regulation, induction of pain, stimulation of bone resorption, and inhibition of immune responses. PGE synthase catalyzes the conversion of PGH₂ to PGE₂. About 25 years ago, Ogino et al [1] reported that glutathione (GSH) was required for the PGE synthase activity, and laid the groundwork for the study of membrane- associated PGE synthase (mPGE synthase). Tanaka et al [2] characterized PGE synthase in sheep vesicular gland microsomes by use of a monoclonal antibody. In 1999, using a clone of microsomal GSH S-transferase 1-like 1, Jakobsson et al [3] expressed human GSH-specific mPGE synthase (mPGE synthase-1) in E. coli. The mPGE synthase-1 had high GSH-dependent PGE synthase activity, and the protein expression was induced by IL-1β. Moreover, Ogorochi et al [4] and Meyer et al [5] independently purified the PGE synthase from the cytosol fraction of human brain and Ascaridia galli, respectively, and reported that the enzyme was GSH S-transferase (GST). Recently Tanioka et al [6] isolated the PGE synthase from the cytosol fraction of rat brain, and reported that the enzyme belonged to GST family.