| Autor: |
Yan K; Beijing Institute of Genomics Chinese Academy of Sciences, Beishan Industrial Zone Shenzhen China., Mei Z; Beijing Institute of Genomics Chinese Academy of Sciences, Beishan Industrial Zone Shenzhen China., Zhao J; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Prodhan MAI; Department of Chemistry University of Louisville KY., Obal D; Department of Anesthesiology and Perioperative and Pain Medicine Stanford University Palo Alto CA., Katragadda K; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Doelling B; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Hoetker D; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Posa DK; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., He L; Department of Chemistry University of Louisville KY., Yin X; Department of Chemistry University of Louisville KY., Shah J; Department of Medicine, Medical college The Aga Khan University Nairobi Kenya., Pan J; Biostatistics Shared Facility University of Louisville Health, Brown Cancer Center Louisville KY., Rai S; Biostatistics Shared Facility University of Louisville Health, Brown Cancer Center Louisville KY., Lorkiewicz PK; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Zhang X; Department of Chemistry University of Louisville KY., Liu S; Beijing Institute of Genomics Chinese Academy of Sciences, Beishan Industrial Zone Shenzhen China., Bhatnagar A; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA., Baba SP; Diabetes and Obesity Center University of Louisville KY.; Christina Lee Brown Envirome Institute University of Louisville KY USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Heart Association [J Am Heart Assoc] 2022 Jul 05; Vol. 11 (13), pp. e023868. Date of Electronic Publication: 2022 Jun 22. |
| DOI: |
10.1161/JAHA.121.023868 |
| Abstrakt: |
Background Histidyl dipeptides such as carnosine are present in a micromolar to millimolar range in mammalian hearts. These dipeptides facilitate glycolysis by proton buffering. They form conjugates with reactive aldehydes, such as acrolein, and attenuate myocardial ischemia-reperfusion injury. Although these dipeptides exhibit multifunctional properties, a composite understanding of their role in the myocardium is lacking. Methods and Results To identify histidyl dipeptide-mediated responses in the heart, we used an integrated triomics approach, which involved genome-wide RNA sequencing, global proteomics, and unbiased metabolomics to identify the effects of cardiospecific transgenic overexpression of the carnosine synthesizing enzyme, carnosine synthase (Carns), in mice. Our result showed that higher myocardial levels of histidyl dipeptides were associated with extensive changes in the levels of several microRNAs, which target the expression of contractile proteins, β-fatty acid oxidation, and citric acid cycle (TCA) enzymes. Global proteomic analysis showed enrichment in the expression of contractile proteins, enzymes of β-fatty acid oxidation, and the TCA in the Carns transgenic heart. Under aerobic conditions, the Carns transgenic hearts had lower levels of short- and long-chain fatty acids as well as the TCA intermediate-succinic acid; whereas, under ischemic conditions, the accumulation of fatty acids and TCA intermediates was significantly attenuated. Integration of multiple data sets suggested that β-fatty acid oxidation and TCA pathways exhibit correlative changes in the Carns transgenic hearts at all 3 levels. Conclusions Taken together, these findings reveal a central role of histidyl dipeptides in coordinated regulation of myocardial structure, function, and energetics. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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