ArticleThe Journal of biological chemistry2011
NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
167 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- The relationship between SIRT1 and inflammation: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.Open forum infectious diseases · 2025Trial
- Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.Shock (Augusta, Ga.) · 2026Article
- Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.Experimental & molecular medicine · 2026Review
- Timing-dependent renal protection of dapagliflozin in endotoxemic diabetic mice by real-time GFR and biomarkers.Intensive care medicine experimental · 2026Article
- A sustained-release depot formulation of β-nicotinamide mononucleotide for alleviating chemotherapy-induced myelosuppression.Materials today. Bio · 2026Article
- SIRT2 Regulates EX VIVO PBMC Adhesion in Septic Shock Patients.Shock (Augusta, Ga.) · 2026Article
- Inhibition of TRPV4 Regulates Mitophagy Through the Sirt1/FoxO1 Signaling Pathway To Alleviate Acute Lung Injury.Inflammation · 2026Article
- Relative suppression of pyroptosis- and necroptosis-related transcriptional programs and enrichment of ferroptosis-related signatures are associated with fatal sepsis: multi-cohort bulk and single-cell transcriptomic evidence.Frontiers in cell and developmental biology · 2026Article
- T-cell dysfunction and death in sepsis: a mechanistic review.Frontiers in immunology · 2026Review
- Aging modulation of the immune system and immunotherapy efficacy in cancer.Frontiers in immunology · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Anti-inflammatory activity and metabolite profiling of myo-inositol in LPS-stimulated macrophages.PloS one · 2026Article
- Integrated Multiomics Analysis and Mendelian Randomization Identify SIRT1 as a Pivotal Aging-Associated Gene in Meningioma.IUBMB life · 2025Article
- The role of the SIRT1 and mTOR pathways in exercise-induced β-cell senescence reduction in type 2 diabetes mellitus.Cellular and molecular life sciences : CMLS · 2025Review
- Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis.Cellular & molecular biology letters · 2025Review
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- AMPK as a Therapeutic Target: Advancing Epilepsy Management Through Metabolic Modulation.Molecular neurobiology · 2025Review
- The Potential of Superoxide Dismutase-RichInternational journal of molecular sciences · 2025Review
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Gene-selective epigenetic reprogramming and shifts in cellular bioenergetics develop when Toll-like receptors (TLR) recognize and respond to systemic life-threatening infections. Using a human monocyte cell model of endotoxin tolerance and human leukocytes from acute systemic inflammation with sepsis, we report that energy sensor sirtuin 1 (SIRT1) coordinates the epigenetic and bioenergy shifts. After TLR4 signaling, SIRT1 rapidly accumulated at the promoters of TNF-α and IL-1β, but not IκBα; SIRT1 promoter binding was dependent on its co-factor, NAD(+). During this initial process, SIRT1 deacetylated RelA/p65 lysine 310 and nucleosomal histone H4 lysine 16 to promote termination of NFκB-dependent transcription. SIRT1 then remained promoter bound and recruited de novo induced RelB, which directed assembly of the mature transcription repressor complex that generates endotoxin tolerance. SIRT1 also promoted de novo expression of RelB. During sustained endotoxin tolerance, nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme for endogenous production of NAD(+), and SIRT1 expression increased. The elevation of SIRT1 required protein stabilization and enhanced translation. To support the coordination of bioenergetics in human sepsis, we observed elevated NAD(+) levels concomitant with SIRT1 and RelB accumulation at the TNF-α promoter of endotoxin tolerant sepsis blood leukocytes. We conclude that TLR4 stimulation and human sepsis activate pathways that couple NAD(+) and its sensor SIRT1 with epigenetic reprogramming.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.