Dimethyl Fumarate Negatively Regulates MYC Signaling and Promotes Cell‐Cycle Arrest in T‐Cells through a GSH‐Dependent Mechanism

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(4)

Published: April 1, 2025

ABSTRACT Recent evidence indicates that the TCA cycle metabolite fumarate plays a specific role in modulating signaling pathways immune cells. We have previously shown dimethyl (DMF) reduces glutathione (GSH) activity and causes accumulation of cellular reactive oxygen species (ROS), thereby compromising effector responses metabolic activities activated T‐cells. However, precise mechanism by which DMF modulates T‐cell remains to be elucidated. This study demonstrates inhibits proliferation, independent receptor (TCR) engagement, this response is fully reversible replenishing GSH. Immunoblot analysis showed had different impacts on TCR downstream decreasing MYC expression while promoting phosphorylation Akt Erk1/2. Cell demonstrated exposure led negative regulation cell cycle‐related proteins induced T‐cells into G0/G1 arrest, was also rescued antioxidants. Several genes related GSH synthesis were upregulated at same time, suggesting potential compensatory may occur reduce oxidative burst following treatment. Our results suggest DMF‐mediated stress alters range pathways, including MYC, leading arrest defective proliferative during activation.

Language: Английский

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Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment

Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

ABSTRACT Cancer is a complex and heterogeneous disease characterised by uncontrolled cell growth proliferation. One hallmark of cancer cells their ability to undergo metabolic reprogramming, which allows them sustain rapid survival. This reprogramming creates an immunosuppressive microenvironment that facilitates tumour progression evasion the immune system. In this article, we review mechanisms underlying in discuss how these alterations contribute establishment microenvironment. We also explore potential therapeutic strategies targeting vulnerabilities enhance immune‐mediated anti‐tumour responses. Trial Registration ClinicalTrials.gov identifier: NCT02044861, NCT03163667, NCT04265534, NCT02071927, NCT02903914, NCT03314935, NCT03361228, NCT03048500, NCT03311308, NCT03800602, NCT04414540, NCT02771626, NCT03994744, NCT03229278, NCT04899921

Language: Английский

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Exploration of circulating metabolic signature of erythrodermic psoriasis based on LC‐MS metabolomics

Experimental Dermatology, Journal Year: 2024, Volume and Issue: 33(5)

Published: May 1, 2024

Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, potential intervention strategies. To gain better understanding mechanisms EP explore serum metabolic signature EP, we conducted an untargeted metabolomics from 20 patients healthy controls. Furthermore, targeted for focused metabolites were identified in samples 30 vulgaris (PsV) patients. In analysis, total 2992 molecular features extracted each sample, peak intensity feature was obtained. Principal component (PCA), orthogonal partial least squares-discriminant (OPLS-DA) revealed significant difference between groups. After screening, 98 found significantly dysregulated including 67 down-regulated 31 up-regulated. had lower levels L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), higher betaine uric acid. KEGG showed differential enriched amino acid metabolism glycerophospholipid metabolism. The L-tryptophan than PsV with negatively correlated PASI scores. discovered. Amino EP. metabolite differences clues they may insights therapeutic interventions.

Language: Английский

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Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders

Molecules, Journal Year: 2024, Volume and Issue: 30(1), P. 56 - 56

Published: Dec. 27, 2024

Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) often discussed in the same physiological pathological situations. The two consecutive initial reactions of BCAA catabolism catalyzed by common enzymes referred to aminotransferase (BCAT) α-keto acid dehydrogenase (BCKDH). BCAT transfers group BCAAs 2-ketoglutarate, which results corresponding 2-keto (BCKAs) glutamate. BCKDH performs an oxidative decarboxylation BCKAs, produces their coenzyme A-conjugates NADH. BCAT2 skeletal muscle dominantly catalyzes transamination BCAAs. Low activity liver reduces metabolization BCAAs, but abundant presence promotes metabolism muscle-derived leads production glucose ketone bodies. While mutations genes responsible for involved rare inherited disorders, aberrant regulation enzymatic activities is associated with major metabolic disorders such diabetes, cardiovascular disease, cancer. Therefore, understanding regulatory process enzymes, well functions metabolites, make a significant contribution our health.

Language: Английский

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Characterization of an aminotransferase TlBCAT from Trichoderma longibrachiatum UN32 involved in dendrobine-type total alkaloids biosynthesis

World Journal of Microbiology and Biotechnology, Journal Year: 2024, Volume and Issue: 40(12)

Published: Nov. 9, 2024

Language: Английский

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Pesticide-induced metabolic disruptions in crops: A global perspective at the molecular level

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 957, P. 177665 - 177665

Published: Dec. 1, 2024

Language: Английский

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