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 |