Inhibition of clotting factor XIII activity by nitric oxide

Maria Valeria Catani, Francesca Bernassola, Antonello Rossi, Gerry Melino

Research output: Contribution to journalArticle

Abstract

The plasma factor XIII (FXIII) is a transglutaminase which catalyzes the cross-linking of fibrin monomers during blood coagulation. S-nitrosylation of protein sulfhydryl groups has been shown to regulate protein function. Therefore, to establish whether nitric oxide (NO) affects the enzymatic activity of FXIII, we studied the effect of the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) in a blood coagulation test in vitro. High concentrations of SNAP were found to have inhibitory effects on clot formation. Moreover, specific formation of γ-dimers through the action of FXIII is selectively inhibited by high concentrations of SNAP, as revealed by Western blot. Purified activated FXIII and plasma preparations were then exposed to NO-donor compounds and the enzyme activity was assayed by measuring the incorporation of [3H] putrescine into dimethylcasein. The NO donors, SNAP, spermine-NO (SPER-NO) and 3-morpholinosydnonimine (SIN-1), and the NO-carrier, S-nitrosoglutathione (GSNO), inhibited FXIII activity in a dose-dependent manner, in both purified enzyme and plasma preparations. Titration of -SH groups of FXIII with [14C] iodoacetamide has shown that the number of titratable cysteines per monomer of FXIII decreased from 1 (in absence of NO donors) to 0 (in the presence of NO donors). These results demonstrate that blood coagulation FXIII is a target for NO both in vitro and in vivo, and that inhibition occurs by S-nitrosylation of a highly reactive cysteine residue. In conclusion, we show that inhibition of FXIII activity by NO may represent an additional regulatory mechanism for the formation of blood clot with physio-pathological implications.

Original languageEnglish
Pages (from-to)275-278
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume249
Issue number1
DOIs
Publication statusPublished - Aug 10 1998

Keywords

  • Factor XIII
  • Nitric oxide
  • S-nitrosylation
  • Transglutaminase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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