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Resveratrol stimulates the metabolic reprogramming of human CD4 + T cells to enhance effector function.
- Source :
-
Science signaling [Sci Signal] 2017 Oct 17; Vol. 10 (501). Date of Electronic Publication: 2017 Oct 17. - Publication Year :
- 2017
-
Abstract
- The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4 <superscript>+</superscript> T cells showed defective antigen receptor signaling and arrest at the G <subscript>1</subscript> stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia-mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest. The concomitant activation of p53 was coupled to the expression of gene products that regulate cell metabolism, leading to a metabolic reprogramming that was characterized by decreased glycolysis, increased glutamine consumption, and a shift to oxidative phosphorylation. These alterations in the bioenergetic homeostasis of CD4 <superscript>+</superscript> T cells resulted in enhanced effector function, with both naïve and memory CD4 <superscript>+</superscript> T cells secreting increased amounts of the inflammatory cytokine interferon-γ. Thus, our data highlight the wide range of metabolic adaptations that CD4 <superscript>+</superscript> T lymphocytes undergo in response to genomic stress.<br /> (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Adult
Antioxidants pharmacology
Ataxia Telangiectasia Mutated Proteins genetics
Ataxia Telangiectasia Mutated Proteins metabolism
CD4-Positive T-Lymphocytes metabolism
Cells, Cultured
Cytokines metabolism
G1 Phase Cell Cycle Checkpoints genetics
Gene Expression Profiling methods
Glycolysis drug effects
Glycolysis genetics
Humans
Oxidative Phosphorylation drug effects
Phosphorylation drug effects
Resveratrol
Signal Transduction genetics
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
CD4-Positive T-Lymphocytes drug effects
DNA Damage
G1 Phase Cell Cycle Checkpoints drug effects
Signal Transduction drug effects
Stilbenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 10
- Issue :
- 501
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 29042482
- Full Text :
- https://doi.org/10.1126/scisignal.aal3024