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Series GSE123596 Query DataSets for GSE123596
Status Public on Mar 06, 2019
Title Collateral DNA damage and NAD+ dependence caused by reactive oxygen species signaling in inflammatory macrophages
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Adoption of Warburg metabolism is critical for macrophage activation in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS (without or with interferon-γ) increase expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ salvage, and loss of NAMPT activity alters their inflammatory potential. However, events leading to NAD+ salvage-dependence in these cells remain poorly defined. We show that NAD+ depletion and increased NAMPT expression occur rapidly after inflammatory activation and coincide with DNA damage caused by reactive oxygen species (ROS). ROS are produced by Complex III of the mitochondrial electron transport chain, and are required for macrophage activation. We show that DNA damage is associated with PARP activation, which results in NAD+ consumption and in this setting increased NAMPT expression allows the maintenance of NAD+ pools sufficient for GAPDH activity and Warburg metabolism. Our findings provide an integrated explanation for dependency on the NAD+ salvage pathway in inflammatory macrophages.
Overall design RNA-seq was performed on bone marrow-derived macrophages (triplicate) exposed to lipopolysaccharide, interferon gamma or interleukin 4.
Contributor(s) Cameron AM, Castoldi A, Sanin DE, Flaschmann LJ, Field CS, Puleston DJ, Kyle RL, Patterson AE, Hässler F, Buescher JM, Kelly B, Pearce EL, Pearce EJ
Citation(s) 30858618, 32796836
Submission date Dec 10, 2018
Last update date Aug 31, 2020
Contact name Immunometabolism Department
Organization name Johns Hopkins University
Department Immunometabolism
Street address 1650 Orleans Street
City Baltimore
State/province Maryland
ZIP/Postal code 21287
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (24)
GSM3507565 LPS_1h_1
GSM3507566 LPS_1h_2
GSM3507567 LPS_1h_3
BioProject PRJNA509296
SRA SRP173259

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Supplementary file Size Download File type/resource
GSE123596_RAW.tar 4.2 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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