Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach

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Lalowski , M M , Björk , S , Finckenberg , P , Soliymani , R , Tarkia , M , Calza , G , Blokhina , D , Tulokas , S , Kankainen , M , Lakkisto , P , Baumann , M , Kankuri , E & Mervaala , E 2018 , ' Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach ' , Frontiers in Physiology , vol. 9 , 365 . https://doi.org/10.3389/fphys.2018.00365

Title: Characterizing the Key Metabolic Pathways of the Neonatal Mouse Heart Using a Quantitative Combinatorial Omics Approach
Author: Lalowski, Maciej M.; Björk, Susann; Finckenberg, Piet; Soliymani, Rabah; Tarkia, Miikka; Calza, Giulio; Blokhina, Daria; Tulokas, Sari; Kankainen, Matti; Lakkisto, Päivi; Baumann, Marc; Kankuri, Esko; Mervaala, Eero
Contributor organization: Medicum
Department of Biochemistry and Developmental Biology
Helsinki Institute of Life Science HiLIFE
Department of Pharmacology
University of Helsinki
Institute for Molecular Medicine Finland
Department of Medical and Clinical Genetics
Clinicum
Department of Clinical Chemistry and Hematology
Marc Baumann / Principal Investigator
Esko Markus Kankuri / Principal Investigator
Eero Mervaala / Principal Investigator
Date: 2018-04-11
Language: eng
Number of pages: 20
Belongs to series: Frontiers in Physiology
ISSN: 1664-042X
DOI: https://doi.org/10.3389/fphys.2018.00365
URI: http://hdl.handle.net/10138/234671
Abstract: The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and beta-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.
Subject: neonatal heart
omics
fructolysis
hypoxia
cardiomyocyte proliferation
regeneration
CARDIAC REGENERATION
CARDIOMYOCYTE PROLIFERATION
MAMMALIAN HEART
NEUROBLASTOMA-CELLS
DISEASE
DIFFERENTIATION
HYPOXIA
PROTEIN
GROWTH
INJURY
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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