RRC ID 47900
著者 Anas AR, Nakajima A, Naruse C, Tone M, Asukabe H, Harada K.
タイトル Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique.
ジャーナル Mar Drugs
Abstract The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this research, we explored different strains of toxic Microcystis aeruginosa and cyanobacteria blooms for the probable fVIIa-soluble Tissue Factor (fVIIa-sTF) inhibitors. The algal cells were subjected to acidification, and reverse phase (ODS) chromatography-solid phase extraction eluted by water to 100% MeOH with 20%-MeOH increments except for M. aeruginosa NIES-89, from the National Institute for Environmental Studies (NIES), which was eluted with 5%-MeOH increments as an isolation procedure to separate aeruginosins 89A and B from co-eluting microcystins. The 40%-80% MeOH fractions of the cyanobacterial extract are active against fVIIa-sTF. The fVIIa-sTF active fractions from cultured cyanobacteria and cyanobacteria blooms were subjected to liquid chromatography-mass spectrometry (LC-MS). The 60% MeOH fraction of M. aeruginosa K139 exhibited an m/z 603 [M + H]⁺ attributed to aeruginosin K139, and the 40% MeOH fraction of M. aeruginosa NIES-89 displayed ions with m/z 617 [M - SO3 + H]⁺ and m/z [M + H]⁺ 717, which attributed to aeruginosin 89. Aeruginosins 102A/B and 298A/B were also observed from other toxic strains of M. aeruginosa with positive fVIIa-sTF inhibitory activity. The active fractions contained cyanobacterial peptides of the aeruginosin class as fVIIa-sTF inhibitors detected by LC-MS.
巻・号 14(1)
ページ 7
公開日 2015-12-30
DOI 10.3390/md14010007
PII md14010007
PMID 26729138
PMC PMC4728504
MeSH Anticoagulants / pharmacology* Chromatography, Liquid Cyanobacteria / chemistry* Factor VIIa / antagonists & inhibitors* Factor VIIa / drug effects Fresh Water Humans Japan Mass Spectrometry Structure-Activity Relationship Thromboplastin / antagonists & inhibitors* Thromboplastin / drug effects
IF 4.073
引用数 4
リソース情報
藻類 NIES-89 NIES-102 NIES-103 NIES-107 NIES-1025 NIES-1058 NIES-1071 NIES-1085 NIES-1099 NIES-1133 NIES-1043 NIES-298