Summary of Study ST002056

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 PR001301. The data can be accessed directly via it's Project DOI: 10.21228/M8JH7P This work is supported by NIH grant, U2C- DK119886.

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Study IDST002056
Study TitleIntegrated Multilayer Omics Reveals the Genomic, Proteomic and Metabolic Influences of the Histidyl Dipeptides on Heart
Study TypeTriomics
Study SummaryHistidyl dipeptides, such as carnosine, present in a micro-millimolar ranges in the heart, are synthesized via the enzyme carnosine synthase (Carns). These dipeptides facilitate glycolysis by proton buffering, form conjugates with reactive aldehydes, such as acrolein, and attenuate ischemia and reperfusion injury. While these dipeptides exhibit multifunctional properties, a composite understanding of their roles in myocardium is lacking. To identify the landscape of histidyl dipeptide mediated responses in the heart, we used a triomics approach of genome wide RNA sequencing, global proteomics and unbiased metabolomics in the cardio specific Carns transgenic (Tg) mice and integrated the three data sets. Our result show higher myocardial levels of histidyl dipeptides lead to extensive changes in several microRNAs, which could target the expression of contractile proteins, beta-fatty acid oxidation and citric acid cycle (TCA) enzymes. Global proteomics shows, expression of contractile proteins, enzymes of beta-fatty acid oxidation and TCA cycle, were enriched in the CarnsTg heart. Under aerobic conditions, the CarnsTg hearts had lower levels of short and long-chain fatty acids and TCA cycle intermediate-succinic acid, whereas, under ischemic conditions the accumulation of fatty acids and TCA cycle intermediates were significantly attenuated in the CarnsTg heart. Integration of multiple data sets suggests that beta-fatty acid oxidation and TCA cycle pathways exhibited correlative changes in the CarnsTg hearts at all three levels. Our triomics approach shows histidyl dipeptides are critical regulators of myocardial structure, function and energetics.
Institute
University of Louisville
Last NameBaba
First NameShahid
Address580 S. Preston St
Emailspbaba01@louisville.edu
Phone5028524274
Submit Date2021-12-15
Num Groups4
Analysis Type DetailGC-MS
Release Date2022-01-31
Release Version1
Shahid Baba Shahid Baba
https://dx.doi.org/10.21228/M8JH7P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003348
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N
Column Agilent DB5-MS (60m × 0.25mm, 0.25um)
MS Type EI
MS instrument type GC x GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode UNSPECIFIED
Units intensity

MS:

MS ID:MS003117
Analysis ID:AN003348
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC x GC-TOF
MS Type:EI
MS Comments:None
Ion Mode:UNSPECIFIED
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