Summary of project PR001301

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.

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

Project ID: PR001301
Project DOI:doi: 10.21228/M8JH7P
Project Title:Integrated multilayer omics reveals the genomic, proteomic and metabolic influences of the histidyl dipeptides on heart
Project Type:Triomics of WT and Carnosin synthase transgenic heart MSTFA dervitization
Project Summary:Histidyl 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
Department:Medicine
Laboratory:Diabetes and Obesity Center
Last Name:Baba
First Name:Shahid
Address:580 S. Preston St
Email:spbaba01@louisville.edu
Phone:5028524274
Funding Source:NIH

Summary of all studies in project PR001301

Study IDStudy TitleSpeciesInstituteAnalysis
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ST002056 Integrated Multilayer Omics Reveals the Genomic, Proteomic and Metabolic Influences of the Histidyl Dipeptides on Heart Mus musculus University of Louisville MS 2022-01-31 1 8 Not available
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