Chiang Nan, Serhan Charles N
Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2006;341:227-50. doi: 10.1385/1-59745-113-4:227.
Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) display beneficial actions in human diseases. The molecular basis for these actions remains of interest. We recently identified novel mediators generated from omega-3 PUFA during cell-cell interactions that displayed potent anti-inflammatory and proresolving actions. Compounds derived from EPA are designated resolvins of the E series (RvE1), and those biosynthesized from DHA are denoted resolvins of the D series (RvD) and docosatriene, such as protectin D1 (PD1), which belongs to the family of protectins. In addition, treatment using aspirin initiates a related epimeric series by triggering endogenous formation of the 17R-RvD series, denoted as aspirin-triggered (AT)-RvDs. These compounds possess potent anti-inflammatory actions in vivo that essentially are equivalent to their counterpart generated without aspirin, namely the 17S-RvDs. In this chapter, we provide an overview and detail protocols of the biosynthesis and bioactions of these newly uncovered pathways and products that include three distinct series: 18R-resolvins of the E series derived from EPA (i.e., RvE1); 17R-resolvins of the D series from DHA (AT-RvD1 through RvD4); and 17S-resolvins of the D series from DHA (RvD1 through RvD4).
ω-3多不饱和脂肪酸(PUFA),如二十碳五烯酸(EPA)和二十二碳六烯酸(DHA),在人类疾病中表现出有益作用。这些作用的分子基础仍备受关注。我们最近在细胞间相互作用过程中发现了由ω-3多不饱和脂肪酸产生的新型介质,它们具有强大的抗炎和促消退作用。源自EPA的化合物被命名为E系列消退素(RvE1),由DHA生物合成的化合物被称为D系列消退素(RvD)和二十二碳三烯,如属于保护素家族的保护素D1(PD1)。此外,使用阿司匹林进行治疗可通过触发17R-RvD系列的内源性形成引发一个相关的差向异构体系列,即阿司匹林触发的(AT)-RvD。这些化合物在体内具有强大的抗炎作用,本质上等同于在没有阿司匹林的情况下产生的对应物,即17S-RvD。在本章中,我们概述并详细介绍了这些新发现的途径和产物的生物合成及生物作用,包括三个不同的系列:源自EPA的E系列18R-消退素(即RvE1);源自DHA的D系列17R-消退素(AT-RvD1至RvD4);以及源自DHA的D系列17S-消退素(RvD1至RvD4)。