Dynamic eicosanoid responses upon different inhibitor and combination   treatments on the arachidonic acid metabolic network

doi:10.1039/c2mb05503a

CORC > 北京大学 > 化学与分子工程学院

	Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network
	He, Chong ; Wu, Yiran ; Lai, Yongquan ; Cai, Zongwei ; Liu, Ying ; Lai, Luhua
刊名	分子生物系统
	2012
关键词	PROSTAGLANDIN E-2 SYNTHASE-1 MECHANISM-BASED INACTIVATION HUMAN WHOLE-BLOOD DEFICIENT MICE POLYMORPHONUCLEAR LEUKOCYTES 5-LIPOXYGENASE 5-LOX CELL-PROLIFERATION TUMOR-ANGIOGENESIS DUAL INHIBITORS DRUG DESIGN
DOI	10.1039/c2mb05503a
英文摘要	The arachidonic acid (AA) metabolic network produces key inflammatory mediators which have been considered as hallmark contributors in various inflammatory related diseases. Enzymes in this network, such as 5-lipoxygenase (5-LOX), cyclooxygenase (COX), leukotriene A(4) hydrolase (LTA4H) and prostaglandin E synthase (PGES), have been used as targets for anti-inflammatory drug discovery. Multi-target drugs and drug combinations have also been developed for this network. However, how the inhibitors alter the dynamics of metabolite production and which combinatorial target intervention solutions are better needs further exploration. We did a system based intervention analysis on the AA metabolic network. Using an LC-MS/MS method, we quantitatively studied the eicosanoid metabolites responses of AA metabolic network during stimulation of Sprague Dawley rat blood samples with the calcium ionophore. Our results indicate that inhibiting the upstream rather than the downstream target of 5-LOX pathway will simultaneously alter the AA metabolism to the COX pathway (and vice versa). Therefore, single-target inhibitors cannot control all the inflammatory mediators at the same time. We also suggest that in the case of multiple-target anti-inflammatory solutions, the combination of inhibitors of the downstream enzymes may have stronger inhibition efficiency and cause less side-effects compared to the other solutions. One therapeutic strategy, LTA4H/COX inhibition solution, was found promising for the intervention of inflammatory mediator biosynthesis and at the same time stimulating the production of anti-inflammatory agents.; Biochemistry & Molecular Biology; SCI(E); 9; ARTICLE; 5; 1585-1594; 8
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/150985]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	He, Chong,Wu, Yiran,Lai, Yongquan,et al. Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network[J]. 分子生物系统,2012.
APA	He, Chong,Wu, Yiran,Lai, Yongquan,Cai, Zongwei,Liu, Ying,&Lai, Luhua.(2012).Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network.分子生物系统.
MLA	He, Chong,et al."Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network".分子生物系统 (2012).