Proteomics

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Activity-based protein profiling in human M2 macrophages using DHA-based photoaffinity probes


ABSTRACT: 17-Hydroxydocosahexaenoic acid (17-HDHA), an oxidative metabolite of the fish oil constituent docosahexaenoic acid (DHA, 22:6 n-3), is a signaling lipid with anti-inflammatory properties. The molecular mechanisms underlying the biological effect of 17-HDHA are poorly understood. Here, we report the design, synthesis and application of a complementary pair of bioorthogonal photoreactive probes based on the polyunsaturated scaffold of 17-HDHA and DHA. In these probes, an alkyne serves as a handle to introduce a fluorescent reporter group or a biotin-affinity tag via copper(I)-catalyzed azide-alkyne cycloaddition. This pair of chemical probes was used to map specific protein interaction partners of 17-HDHA in primary human macrophages, which led to the identification of prostaglandin reductase 1 (PTGR1) as a target of 17-HDHA, but not DHA. Ensuing biochemical studies revealed that PTGR1 converted 17-HDHA into 17-oxo-DHA, which inhibited the biosynthesis of the pro-inflammatory lipids 5-HETE and LTB4 in human macrophages and neutrophils.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Macrophage

DISEASE(S): Disease Free

SUBMITTER: Berend Gagestein  

LAB HEAD: Mario van der Stelt

PROVIDER: PXD027600 | Pride | 2023-04-28

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20181008_BEGA2-034_01.raw.7z Raw
20181008_BEGA2-034_02.raw.7z Raw
20181008_BEGA2-034_03.raw.7z Raw
20181008_BEGA2-034_04.raw.7z Raw
20181008_BEGA2-034_05.raw.7z Raw
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Publications

Comparative Photoaffinity Profiling of Omega-3 Signaling Lipid Probes Reveals Prostaglandin Reductase 1 as a Metabolic Hub in Human Macrophages.

Gagestein Berend B   von Hegedus Johannes H JH   Kwekkeboom Joanneke C JC   Heijink Marieke M   Blomberg Niek N   van der Wel Tom T   Florea Bogdan I BI   van den Elst Hans H   Wals Kim K   Overkleeft Herman S HS   Giera Martin M   Toes René E M REM   Ioan-Facsinay Andreea A   van der Stelt Mario M  

Journal of the American Chemical Society 20221005 41


The fish oil constituent docosahexaenoic acid (DHA, 22:6 n-3) is a signaling lipid with anti-inflammatory properties. The molecular mechanisms underlying the biological effect of DHA are poorly understood. Here, we report the design, synthesis, and application of a complementary pair of bio-orthogonal, photoreactive probes based on the polyunsaturated scaffold DHA and its oxidative metabolite 17-hydroxydocosahexaenoic acid (17-HDHA). In these probes, an alkyne serves as a handle to introduce a f  ...[more]

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