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Fibrinogen is a heme-associated, carbon monoxide sensing molecule: a preliminary report.

Abstract
The objective of this study was to determine how carbon monoxide directly modifies fibrinogen utilizing liquid chromatography-mass spectrometry (LC-MS/MS) by examining fibrinogen exposed to carbon monoxide releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer; CORM-2]. Purified fibrinogen was exposed to 0, 25, 50 or 100 μmol/l CORM-2 for 5 min at 37°C and then stored at -80°C before analyses with LC-MS/MS. In a second series of experiments, normal plasma was exposed to 0 or 100 μmol/l CORM-2 in the absence or presence of the nitric oxide donor sodium nitroprusside and hydroquinone (an organic reductant) to compete with carbon monoxide binding to a putative heme group found on fibrinogen. Coagulation was activated with tissue factor (n=8 per condition). Thrombus growth was monitored with thrombelastography for 15 min. LC-MS/MS did not detect any direct modifications of amino acids in fibrinogen, but detection of small regions of both the alpha and gamma chains was lost following exposure to CORM-2 and endoproteinase digestion with trypsin and Glu-C. An ion with the same m/z and expected retention time as heme was found in the purified fibrinogen. Exposure of plasma to nitric oxide/hydroquinone significantly decreased CORM-2-mediated enhancement of coagulation without affecting the coagulation kinetics of plasma not exposed to CORM-2. Carbon monoxide derived from CORM-2 likely modifies fibrinogen via modulation of a fibrinogen-associated heme group(s). Whereas the precise molecular location of heme attachment and three-dimensional conformational change secondary to carbon monoxide exposure remain to be determined, fibrinogen appears to be a carbon monoxide sensing molecule.
AuthorsVance G Nielsen, Jack B Cohen, S Nini Malayaman, Mathew Nowak, Keith Vosseller
JournalBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 22 Issue 5 Pg. 443-7 (Jul 2011) ISSN: 1473-5733 [Electronic] England
PMID21451399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Organometallic Compounds
  • tricarbonyldichlororuthenium (II) dimer
  • Heme
  • Carbon Monoxide
  • Fibrinogen
Topics
  • Blood Coagulation
  • Carbon Monoxide (metabolism)
  • Fibrinogen (metabolism)
  • Heme (metabolism)
  • Humans
  • Kinetics
  • Organometallic Compounds (pharmacology)
  • Plasma
  • Tandem Mass Spectrometry
  • Thrombelastography
  • Thrombosis

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