Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart.
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. Alth...
| Publicado en: | Journal of the American Heart Association Vol. 11; no. 13; pp. 1 - 21 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
7/5/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158000976&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158000976 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20479980 FSQ9 jtl: Journal of the American Heart Association issn: 20479980 maglogo: Y pubinfo: dt: 7/5/2022 vid: 11 iid: 13 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 158000976 158000976 NLM35730646 158000976 10.1161/JAHA.121.023868 NLM35730646 158000976 ppf: 1 ppct: 20 formats: tig: atl: Integrated Multilayer Omics Reveals the Genomic, Proteomic, and Metabolic Influences of Histidyl Dipeptides on the Heart. aug: au: Keqiang Yan Zhanlong Mei Jingjing Zhao Islam Prodhan, Md Aminul Detlef Obal Katragadda, Kartik Doelling, Benjamin Hoetker, David Posa, Dheeraj Kumar Liqing He Xinmin Yin Shah, Jasmit Jianmin Pan Rai, Shesh Lorkiewicz, Pawel Konrad Xiang Zhang Siqi Liu Bhatnagar, Aruni Baba, Shahid P. Yan, Keqiang affil: Beijing Institute of Genomics,, Chinese Academy of Sciences, Beishan Industrial Zone,, Shenzhen,, China. sug: subj: Oligopeptides Oligopeptides Pharmacodynamics Oligopeptides Metabolism Proteomics Mice Contractile Proteins Metabolism Oxidation-Reduction Myocardium Metabolism Fatty Acids Metabolism Mammals Metabolism Animals Short Portable Mental Status Questionnaire Scales ab: 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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