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 ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
---|---|---|---|---|---|---|---|---|
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 |