イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Acid-activated prorenin binds to (pro)renin receptor in vitro.
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：1090-2104(Electronic)0006-291X(Linking)
巻・号・頁	428(4),pp.506-11
著者・共著者	Nabi A H M Nurun†, Biswas Kazal Boron, Nasrin Haque K M, ARAI Yoshie, NAKAGAWA Tsutomu, EBIHARA Akio, ICHIHARA Atsuhiro, INAGAMI Tadashi, SUZUKI Fumiaki*
発行年月	2012/11
概要	Binding properties of acid-activated prorenin to (pro)renin receptor [(P)RR]was investigated in vitro to discuss possible roles of such reversibly acid-activated prorenin in the renin angiotensin (RA) system. Prorenin was acidified at pH 3.3, 4.5, 5.5, 6.5, and its activation level was measured at 1, 2, 4, 8, 12, and 25 h. Prorenin, activated non-proteolytically in time- and pH-dependent manners, was verified by Western blot analyses. Acidification of prorenin for 25 h at pH 3.3, 4.5, 5.5, and 6.5 showed 78%, 54%, 34%, and 20% activities, respectively when compared with the renin activity of trypsinized prorenin as 100%. Additionally, the binding properties of acidified prorenin to (P)RR were elucidated both at the equilibrium state and in the kinetic state using BIAcore. BIAcore assay showed that acidified prorenin at pH 3.3, 4.5, 5.5, and 6.5 had apparent K(D) of 1.57 × 10(4), 14.1, 8.29, and 8.04 nM, respectively while native prorenin at pH 7.4 had a K(D) of 7.8 nM. At equilibrium state, K(D) of native prorenin was 1.42 nM whereas apparent K(D) varied from 1.25 to 5.0 nM for the prorenin acidified at pH 4.5, 5.5, and 6.5. The K(m) values of free forms of acidified prorenin at different pH (0.33-0.5 μM) was almost similar to those of (P)RR-bound forms of acidified prorenin (0.5-0.77 μM). These in vitro data indicate that prorenin acidified in vivo possibly modulate RA system in receptor-dependent and/or -independent manners which could ultimately lead to the pathogenesis of diseases.
DOI	10.1016/j.bbrc.2012.10.075
文献番号	23111329