S-Nitrosylated human α1-protease inhibitor

Yoichi Miyamoto, Takaaki Akaike, Hiroshi Maeda

研究成果: Review article査読

37 被引用数 (Scopus)

抄録

α1-Protease inhibitor (α1PI) is an acute phase plasma protein, and possesses a single cysteine residue at position 232. A single cysteinyl sulfhydryl of human α1PI is found to be readily S-nitrosylated by nitric oxide (NO) in vitro without affecting the inhibitory capacity against bovine trypsin or elastase, a major target protease of α1PI in vivo. S-Nitroso-α1PI (S-NO-α1PI) was also formed by the reaction of α1PI with NO produced excessively by a murine macrophage cell line (RAW264 cells) upon infection with Salmonella typhimurium and in an ex vivo perfusion system of the liver obtained from lipopolysaccharide-treated rats. S-NO-α1PI (10-9-10-6 M) induces a dose-dependent relaxation of the ring preparation of rabbit aorta. Also, S-NO-α1PI but not α1PI shows a potent inhibitory effect on platelet aggregation. Unprecedented observation is that S-NO-α1PI showed a potent bacteriostatic effect against a wide range of bacteria at the concentration of 1-10 μM, which was 10-1000-fold stronger than that of NO and other S-nitrosylated compounds including S-nitrosylated albumin and S-nitrosylated glutathione. These results suggest that S-NO-α1PI is produced as an NO sink under inflammatory conditions, where production of both α1PI and NO is highly up-regulated, and it may function as a soluble factor which consists of an innate defense system through not only the protease inhibitory activity but also its antibacterial activity and facilitating the peripheral blood flow. Therefore, S-nitrosylation of α1PI occurring under physiological conditions in vivo should diversify the biological functions contributing to cytoprotective effects of α1PI. Copyright (C) 2000 Elsevier Science B.V.

本文言語English
ページ(範囲)90-97
ページ数8
ジャーナルBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
1477
1-2
DOI
出版ステータスPublished - 2000 3 7
外部発表はい

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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