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제114회 대한화학회 학술발표회, 총회 및 기기전시회 안내 LC-MS-based in-vitro quantitative eicosanoid signatures on inflammatory responses of simvastatin

2014년 8월 13일 15시 15분 51초
ANAL.P-494 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
10월 15일 (수요일) 16:00~19:00
저자 및
이수현, 이원용, 정봉철1, 최만호1,*
연세대학교 화학과, Korea
1한국과학기술연구원(KIST) 분자인식연구센터, Korea
Statins reduce low-density lipoprotein cholesterol in the mevalonate pathway and one of their pleiotropic effects, anti-inflammation, have been concerned with additional benefits of the clinical outcomes preventing cardiovascular events. Eicosanoids are oxygenated metabolites of membrane-released arachidonic acid through the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 ω-hydroxylase (CYP ω-hydroxylase) and non-enzymatic free radicals. In contrast to the conventional circulating inflammation markers, evaluating the broad spectrum of lipid signaling mediators may give better understanding the biological functions of inflammation. A liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling in the liver microsomal S9 fractions have been developed to measure 33 eicosanoids in the liver S9 fraction. The limit of quantification is 0.5~20 ng/mg proteins, while the precision (% CV) and accuracy (% bias) ranges from 4.7 to 10.8% and from 88.4 to 110.9%, respectively. Eicosanoid signatures resulted in the COX metabolites were increased in inflammation-induced model rabbits against the control rabbits, whereas 20-HETE catalyzed by CYP ω-hydroxylase was significantly decreased. In contrast, all detected eicosanoids catalyzed by COXs and LOXs showed no significant alterations, whereas the levels of 20-HETE were significantly increased (9.33- and 11.85-folds in response to 50 and 100 μM treatments, respectively; P<0.001) after simvastatin treatment. The devised method shows a new insight of anti-inflammation mechanism of statins and could be a useful tool for evaluation of drug efficacies and physiological changes in inflammation.