Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis.
The molecular basis for the beneficial impact of essential omega-3 fatty acids is of considerable interest. Recently, novel mediators generated from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that displayed potent bioactions were first identified in resolving inflammatory exudates [J. Exp. Med. 192 (2000) 1197; J. Exp. Med. 196 (2002) 1025] and in tissues enriched with DHA [J. Exp. Med. 196 (2002) 1025; J. Biol. Chem. 278 (2003) 14677]. The trivial names Resolvin (resolution phase interaction products) and docosatrienes were introduced for the bioactive compounds belonging to these novel series because they demonstrate potent anti-inflammatory and immunoregulatory actions. The compounds derived from eicosapentaenoic acid carrying potent biological actions (i.e., 1-10 nM range) are designated E series, given their EPA precursor, and denoted as Resolvins of the E series (Resolvin E1 or RvE1), and those biosynthesized from the precursor docosahexaenoic acid are Resolvins of the D series (Resolvin D1 or RvD1). Bioactive members from DHA with conjugated triene structures are docosatrienes (DT) that are immunoregulatory [J. Exp. Med. 196 (2002) 1025; J. Biol. Chem. 278 (2003) 14677], and neuroprotective [J. Biol. Chem., 278 (2003) 43807; Proc. Natl. Acad. Sci. U.S.A. [submitted for publication]] and are termed neuroprotectins. The specific receptors for these novel bioactive products from omega-3 EPA and DHA are abbreviated Resolvin D receptors (i.e., ResoDR1), Resolvin E receptor (ResoER1; RER1), and neuroprotectin D receptors (NPDR), respectively, in recognition of their respective cognate ligands. Aspirin treatment impacts biosynthesis of these compounds and a related series by triggering endogenous formation of the 17R-D series Resolvins and docosatrienes. These novel epimers are denoted as aspirin-triggered (AT)-RvDs and -DTs, and possess potent anti-inflammatory actions in vivo essentially equivalent to their 17S series pathway products. Here, we provide a syntomy overview of the formation and actions of these newly uncovered pathways and products as well as highlight their role(s) as endogenous protective mediators generated in anti-inflammation and catabasis.
Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. cnserhan@zeus.bwh.harvard.edu
Charles N
CN
Serhan
Katherine
K
Gotlinger
Song
S
Hong
Makoto
M
Arita
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D001241:Aspirin