Biosynthesis of maresin conjugates in tissue regeneration (MCTR)

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Homo sapiens
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Resolution of inflammation is carried out by endogenous mediators termed specialised proresolving mediators (SPMs). Macrophages are central to the acute inflammatory response, governing both initiation and resolution phases, depending on the macrophage subtype activated. Human macrophages involved in resolution produce a family of bioactive peptide-conjugated mediators called maresin conjugates in tissue regeneration (MCTR). These mediators stimulate human phagocytotic functions, promote the resolution of bacterial infections, counterregulate the production of proinflammatory mediators and promote tissue repair and regeneration (Dalli et al. 2016). The proposed biosynthetic pathway is as follows. The maresin epoxide intermediate 13(S),14(S)-epoxy-MaR (13(S),14(S)-epoxy-docosahexaenoic acid) can be converted to MCTR1 (13(R)-glutathionyl, 14(S)-hydroxy-docosahexaenoic acid) by LTC4S and GSTM4. MCTR1 can be converted to MCTR2 (13(R)-cysteinylglycinyl, 14(S)-hydroxy-docosahexaenoic acid) by γ-glutamyl transferase (GGT). Finally, a dipeptidase can cleave the cysteinyl-glycinyl bond of MCTR2 to give MCTR3 (13(R)-cysteinyl, 14(S)-hydroxy-docosahexaenoic acid) (Dalli et al. 2016, Serhan et al. 2017).
Literature References
PubMed ID Title Journal Year
27791009 Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages

Riley, IR, Serhan, CN, Rodriguez, AR, Petasis, NA, Chiang, N, Spur, BW, Vlasakov, I, Dalli, J

Proc. Natl. Acad. Sci. U.S.A. 2016
28802833 New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration

Serhan, CN, Chiang, N, Dalli, J

Mol. Aspects Med. 2017
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