Summary of Study ST000172

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000149. The data can be accessed directly via it's Project DOI: 10.21228/M8Q59J This work is supported by NIH grant, U2C- DK119886.

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Study IDST000172
Study TitleTHP1 Human Monocyte cells Project A (part I)
Study SummaryCitrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0•4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1•4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8–luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response. Research is published, core data not used but project description is relevant: http://onlinelibrary.wiley.com/doi/10.1111/cei.12591/full
Institute
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
Submit Date2015-06-04
Num Groups15
Total Subjects59
Raw Data AvailableYes
Raw Data File Type(s)cdf
Uploaded File Size2.4 G
Analysis Type DetailLC-MS
Release Date2015-12-28
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8Q59J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000149
Project DOI:doi: 10.21228/M8Q59J
Project Title:Citrate Flux Studies
Project Summary:Citrate Flux analysis
Institute:University of Michigan
Department:Pediatric Nephrology
Laboratory:Blatt Lab
Last Name:Blatt
First Name:Neal
Address:Ann Arbor, MI
Email:nblatt@umich.edu
Phone:734/936-4210

Subject:

Subject ID:SU000191
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id 13C6 Citrate (mM) LPS (Time) Citrate (mM)
SA009376S000135741 0 none
SA009377S000135731 0 none
SA009378S000135721 0 none
SA009379S000135711 0 none
SA009380S000135901 1 h none
SA009381S000135881 1 h none
SA009382S000135871 1 h none
SA009383S000135891 1 h none
SA009384S000135821 30 min none
SA009385S000135811 30 min none
SA009386S000135791 30 min none
SA009387S000135801 30 min none
SA009388S000135706 0 none
SA009389S000135696 0 none
SA009390S000135676 0 none
SA009391S000135686 0 none
SA009392S000135846 1 h none
SA009393S000135836 1 h none
SA009394S000135866 1 h none
SA009395S000135856 1 h none
SA009396S000135776 30 min none
SA009397S000135766 30 min none
SA009398S000135756 30 min none
SA009399S000135786 30 min none
SA009400S00013540none 0 0
SA009401S00013543none 0 0
SA009402S00013542none 0 0
SA009403S00013541none 0 0
SA009404S00013536none 0 1
SA009405S00013537none 0 1
SA009406S00013539none 0 1
SA009407S00013538none 0 1
SA009408S00013535none 0 6
SA009409S00013534none 0 6
SA009410S00013533none 0 6
SA009411S00013532none 0 6
SA009412S00013563none 1 h 0
SA009413S00013565none 1 h 0
SA009414S00013566none 1 h 0
SA009415S00013564none 1 h 0
SA009416S00013561none 1 h 1
SA009417S00013562none 1 h 1
SA009418S00013560none 1 h 1
SA009419S00013557none 1 h 6
SA009420S00013556none 1 h 6
SA009421S00013558none 1 h 6
SA009422S00013559none 1 h 6
SA009423S00013552none 30 min 0
SA009424S00013553none 30 min 0
SA009425S00013554none 30 min 0
SA009426S00013555none 30 min 0
SA009427S00013548none 30 min 1
SA009428S00013549none 30 min 1
SA009429S00013550none 30 min 1
SA009430S00013551none 30 min 1
SA009431S00013544none 30 min 6
SA009432S00013545none 30 min 6
SA009433S00013547none 30 min 6
SA009434S00013546none 30 min 6
Showing results 1 to 59 of 59

Collection:

Collection ID:CO000178
Collection Summary:-
Sample Type:Monocytes

Treatment:

Treatment ID:TR000198

Sample Preparation:

Sampleprep ID:SP000192
Sampleprep Summary:-
Sampleprep Protocol Filename:Gly-TCA-nucleotides_analysis_protocol-2015-03-09.docx

Combined analysis:

Analysis ID AN000266
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1260
Column Phenomenex Luna NH2 (150 x 1mm,3um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6520 QTOF
Ion Mode NEGATIVE
Units Area normalized to protein

Chromatography:

Chromatography ID:CH000189
Methods ID:AQM020
Methods Filename:QTOF-002-HILIC-35min-1mm-No_Insert.m.zip
Instrument Name:Agilent 1260
Column Name:Phenomenex Luna NH2 (150 x 1mm,3um)
Chromatography Type:HILIC

MS:

MS ID:MS000215
Analysis ID:AN000266
Instrument Name:Agilent 6520 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
Acquisition Parameters File:QTOF-002-HILIC-35min-1mm-No_Insert.m.zip
Processing Parameters File:EX00268-flux-MassHunterQuant-GlyTCA-LCMS-DataAnalysis-Method.m.zip
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