Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization.

Autor:	Sowers ML; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA., Tang H; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA., Singh VK; Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, Texas, USA., Khan A; Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, Texas, USA., Mishra A; Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, Texas, USA., Restrepo BI; University of Texas Health Science Center at Houston, School of Public Health, Brownsville, Texas, USA., Jagannath C; Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, Texas, USA. Electronic address: cjagannath@houstonmethodist.org., Zhang K; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: kazhang@utmb.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2022 Oct; Vol. 298 (10), pp. 102418. Date of Electronic Publication: 2022 Aug 27.
DOI:	10.1016/j.jbc.2022.102418
Abstrakt:	Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood-derived monocytes into either 'proinflammatory M1-' or 'anti-inflammatory M2-' MФs. We report here a complex relationship between arginine, tryptophan, glucose, and the citric acid cycle metabolism, protein and histone post-translational modifications, and human macrophage polarization that was previously not described. Surprisingly, M1-MФs had globally reduced histone acetylation levels but high levels of acetylated amino acids. This suggests acetyl-CoA was diverted, in part, toward acetylated amino acids. Consistent with this, stable isotope tracing of glucose revealed reduced usage of acetyl-CoA for histone acetylation in M1-MФs. Furthermore, isotope tracing also revealed MФs uncoupled glycolysis from the tricarboxylic acid cycle, as evidenced by poor isotope enrichment of succinate. M2-MФs had high levels of kynurenine and serotonin, which are reported to have immune-suppressive effects. Kynurenine is upstream of de novo NAD + metabolism that is a necessary cofactor for Sirtuin-type histone deacetylases. Taken together, we demonstrate a complex interplay between metabolism and epigenetics that may ultimately influence cell phenotype. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu