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

doi:10.1039/c2mb05503a

CORC > 化学研究所 > 中国科学院化学研究所

	Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network
	He, Chong 1,2,3; Wu, Yiran 1,2,3; Lai, Yongquan 4; Cai, Zongwei 4; Liu, Ying 1,2,3; Lai, Luhua 1,2,3
刊名	MOLECULAR BIOSYSTEMS
	2012
卷号	8 期号:5 页码:1585-1594
ISSN号	1742-206X
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.
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000302368600023
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/48327]
专题	中国科学院化学研究所
通讯作者	Lai, Luhua
作者单位	1.Peking Univ, BNLMS, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China 2.Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China 3.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China 4.Hong Kong Baptist Univ, Dept Chem, Hong Kong, Hong Kong, Peoples R China
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]. MOLECULAR BIOSYSTEMS,2012,8(5):1585-1594.
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.MOLECULAR BIOSYSTEMS,8(5),1585-1594.
MLA	He, Chong,et al."Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network".MOLECULAR BIOSYSTEMS 8.5(2012):1585-1594.