Novel functions of human α1-protease inhibitor after S-nitrosylation: Inhibition of cysteine protease and antibacterial activity

Yoichi Miyamoto, Takaaki Akaike, M. Samiul Alam, Katsuhisa Inoue, Takayoshi Hamamoto, Norisato Ikebe, Jun Yoshitake, Tatsuya Okamoto, Hiroshi Maeda

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

α1-Protease inhibitor (α1PI), the most abundant serine protease inhibitor found in human plasma (at 30-60 μM), is a glycoprotein (53 kDa) having a single cysteine residue at position 232 (Cys232). We have found that Cys232 of human α1PI was readily S-nitrosylated by nitric oxide (NO) without affecting inhibitory activity to trypsin or elastase. S-nitrosylated α1PI (S-NO-α1PI) not only retained inhibitory activity against these serine proteases, but also gained thiol protease inhibitory activity against a Streptococcus pyogenes protease; the parental α1PI did not have this activity. Furthermore, S-NO-α1PI exhibited bacteriostatic activity against Salmonella typhimurium at concentrations of 0.1-10 μM, which were 20- to 3000-fold stronger than those of the other NO-generating compounds or S-nitroso compounds such as S-nitrosoalbumin and S-nitrosoglutathione. NO appears to be transferred into the bacterial cells from S-NO-α1PI via transnitrosylation, as evidenced by electron spin resonance spectroscopy with an NO spin trap. Thus, we conclude that S-NO-α1PI may be generated from the reaction between α1PI and NO under inflammatory conditions, in which production of both is known to increase. As a result, new functions, i.e., antibacterial and thiol protease inhibitory activities of α1PI, were generated. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)918-923
Number of pages6
JournalBiochemical and biophysical research communications
Volume267
Issue number3
DOIs
Publication statusPublished - 2000 Jan 27
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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