Summary of study ST000202

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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000202
Study TitleTHP1 Human Monocyte cells Project A (part II)
Study TypeGlycolysis/TCA/Nucleotide analysis (tissue/cells)
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 Date2015-06-11
Num Groups15
Total Subjects59
Raw Data AvailableYes
Raw Data File Type(s).xml,.xsd,.stg, .bin, .cd,.cG
Uploaded File Size4.3 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

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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:SU000221
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)
SA010070S000135741 0 none
SA010071S000135731 0 none
SA010072S000135721 0 none
SA010073S000135711 0 none
SA010074S000135901 1 h none
SA010075S000135881 1 h none
SA010076S000135871 1 h none
SA010077S000135891 1 h none
SA010078S000135821 30 min none
SA010079S000135811 30 min none
SA010080S000135791 30 min none
SA010081S000135801 30 min none
SA010082S000135706 0 none
SA010083S000135696 0 none
SA010084S000135676 0 none
SA010085S000135686 0 none
SA010086S000135846 1 h none
SA010087S000135836 1 h none
SA010088S000135866 1 h none
SA010089S000135856 1 h none
SA010090S000135776 30 min none
SA010091S000135766 30 min none
SA010092S000135756 30 min none
SA010093S000135786 30 min none
SA010094S00013540none 0 0
SA010095S00013543none 0 0
SA010096S00013542none 0 0
SA010097S00013541none 0 0
SA010098S00013536none 0 1
SA010099S00013537none 0 1
SA010100S00013539none 0 1
SA010101S00013538none 0 1
SA010102S00013535none 0 6
SA010103S00013534none 0 6
SA010104S00013533none 0 6
SA010105S00013532none 0 6
SA010106S00013563none 1 h 0
SA010107S00013565none 1 h 0
SA010108S00013566none 1 h 0
SA010109S00013564none 1 h 0
SA010110S00013561none 1 h 1
SA010111S00013562none 1 h 1
SA010112S00013560none 1 h 1
SA010113S00013557none 1 h 6
SA010114S00013556none 1 h 6
SA010115S00013558none 1 h 6
SA010116S00013559none 1 h 6
SA010117S00013552none 30 min 0
SA010118S00013553none 30 min 0
SA010119S00013554none 30 min 0
SA010120S00013555none 30 min 0
SA010121S00013548none 30 min 1
SA010122S00013549none 30 min 1
SA010123S00013550none 30 min 1
SA010124S00013551none 30 min 1
SA010125S00013544none 30 min 6
SA010126S00013545none 30 min 6
SA010127S00013547none 30 min 6
SA010128S00013546none 30 min 6
Showing results 1 to 59 of 59

Collection:

Collection ID:CO000209
Sample Type:Monocytes

Treatment:

Treatment ID:TR000229

Sample Preparation:

Sampleprep ID:SP000223
Sampleprep Protocol Filename:Gly-TCA-nucleotides_analysis_protocol-2015-03-09.docx

Combined analysis:

Analysis ID AN000304
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:CH000225
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:MS000253
Analysis ID:AN000304
Instrument Name:Agilent 6520 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
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