Chemoproteomic Profiling of Itaconation by Bioorthogonal Probes in Inflammatory Macrophages

Itaconate is an anti-inflammatory metabolite involved in pathogen–macrophage interactions, but the mechanisms underlying its effect are not fully understood. Competitive cysteine profiling has been performed to interrogate itaconate’s reactivity in cell lysates, but methods for analyzing targets of...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-06, Vol.142 (25), p.10894-10898
Main Authors: Qin, Wei, Zhang, Yanling, Tang, Huan, Liu, Dongyang, Chen, Ying, Liu, Yuan, Wang, Chu
Format: Article
Language:English
Subjects:
A549 Cells
Alkynes - chemistry
Alkynes - pharmacology
Animals
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Cysteine - chemistry
Cysteine - metabolism
Glutathione - chemistry
Glutathione - metabolism
Humans
Macrophages - metabolism
Mice
Molecular Probes - chemistry
Molecular Probes - pharmacology
Proteins - chemistry
Proteins - metabolism
Proteomics - methods
RAW 264.7 Cells
Succinates - chemistry
Succinates - pharmacology
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Summary:Itaconate is an anti-inflammatory metabolite involved in pathogen–macrophage interactions, but the mechanisms underlying its effect are not fully understood. Competitive cysteine profiling has been performed to interrogate itaconate’s reactivity in cell lysates, but methods for analyzing targets of itaconation directly in living macrophages are still lacking. In this work, we developed a specific bioorthogonal probe, itaconate–alkyne (ITalk), for quantitative and site-specific chemoproteomic profiling of itaconation in inflammatory macrophages. ITalk recapitulates the anti-inflammatory property of itaconate and enables biochemical evaluation and proteomic analysis of its direct targets. Our study delineates the widespread landscape of itaconate substrates, providing a versatile tool and comprehensive resource for investigating its function.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b11962