Effect of l-ethionine on macromolecular synthesis in mitogen-stimulated lymphocytes

Zabos, Peter; Kyner, David; Seide-Kehoe, Rochelle; Acs, George; Christman, Judith K.

doi:10.1016/0005-2787(78)90015-1

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…The immunomodulatory effect was preserved when the diet contained enough methionine to prevent nonimmunologic phenotypes (36). Investigation of lymphocytes showed reduced blasting and proliferation upon stimulation with phytohemaglutinin or concavalin A, when they were pretreated with ethionine (37). Similarly, we found that in the presence of ethionine, the monocytic THP-1 cell line had a reduced expression of the inflammatory cytokines, probably via reduced activation of the NF-kB pathway.…”

Section: Discussionsupporting

confidence: 67%

“…Few data are present that indicate the involvement of ethionine in the ethylation of lysines. Experiments that used radioactively labeled ethionine in in vitro methylation assays remained inconclusive (37). However, MS of histones showed that ethylation of lysine residues is a novel modification.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports mention potential anti-inflammatory properties of the unconventional amino acid ethionine (36)(37)(38). Accordingly, we conducted a cell-based bio assay to assess this immunomodulatory effect.…”

Section: Reuteri Produces the Immunomodulatory Metabolite Ethioninementioning

confidence: 99%

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Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Röth

Chiang

et al. 2018

FASEB j.

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Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1‐carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2‐carbon‐transporting folate in the form of 5, 10‐ethenyl‐tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2‐carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP‐1 cells with ethionine, their transcription of TNF‐α was inhibited and cell proliferation reduced. Mass spectrometry of THP‐1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone‐methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2‐carbon transporting variant of the folate cycle and modify human chromatin via ethylation.—Roth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. FASEB J. 33,3536‐3548 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Röth

Chiang

et al. 2018

FASEB j.

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“…8, 3, panels A and B). In contrast, experiments with ethionine, a reversible growth-inhibiting agent for lymphocytes [49], showed reversible growth inhibition ( Fig. 8, 4, panels A and B).…”

Section: Irreversibility Of Growth Inhibition Induced In Beas-2b Cellmentioning

confidence: 87%

Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation

Ke¹,

Reddel²,

Gerwin³

et al. 1988

Differentiation

160

100

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“…However, morphological changes characteristic of lymphoblast formation and complete commitment to DNA synthesis can occur in the presence of ethionine, even though the synthesis of DNA is blocked. Thus, ethionine permits a quiescent lymphocyte to enter the Gl stage of the cell cycle and to progress toward the S phase (221).…”

Section: Inhibition Of Deoxyribonucleic Acidmentioning

confidence: 99%

Molecular aspects of the in vivo and in vitro effects of ethionine, an analog of methionine.

Alix¹

1982

Microbiological Reviews

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Effect of l-ethionine on macromolecular synthesis in mitogen-stimulated lymphocytes

Cited by 13 publications

References 24 publications

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Two‐carbon folate cycle of commensalLactobacillus reuteri6475 gives rise to immunomodulatory ethionine, a source for histone ethylation

Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation

Molecular aspects of the in vivo and in vitro effects of ethionine, an analog of methionine.

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