Journal Article Ppublish 1 citation
PubMed: 42455463 DOI: 10.1096/fj.202504676R
Carnosine-Related Metabolism in Rat Cardiomyocytes and Human Heart Tissue.
FASEB J 40(14):e72033
Authors: Jade V Creighton, Lívia de Souza Gonçalves, Saulo Gil, Bianca Scigliano Vargas, Leonardo Jensen, Marisa Helena Gennari de Medeiros, Hamilton Roschel, Mark D Turner, Craig L Doig, Guilherme Giannini Artioli, Craig Sale
Affiliations
- Centre for Systems Health and Integrated Metabolic Research (SHiMR), School of Science and Technology, Nottingham Trent University, Nottingham, UK.
- Department of Pediatrics, Division of Pediatric, University of California, San Francisco, California, USA.
- Applied Physiology & Nutrition Research Group, School of Physical Education and Sport, Faculdade de Medicina, Divisão de Reumatologia, Universidade de São Paulo, São Paulo, Brazil.
- Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
- Laboratorio de Hipertensao do Instituto do Coraçao do Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
- Department of Sport and Exercise Sciences, Manchester Metropolitan University Institute of Sport, Manchester, UK.
Abstract
The therapeutic potential of carnosine in healthy and diseased heart models is promising; however, the understanding of carnosine and β-alanine metabolism in cardiac tissue is lacking. Exploring how these compounds are metabolized in cardiac tissue is critical to determine their viability for in vivo supplementation studies. Two independent studies were conducted. Study 1 investigated the uptake of exogenous carnosine and β-alanine in cardiomyocytes and the influence of this on the expression of carnosine- and β-alanine-related enzyme and transporter genes. Study 2 investigated whether human cardiac tissue expresses carnosine and β-alanine metabolism proteins and the endogenous concentrations of carnosine and β-alanine. In Study 1, differentiated H9c2 cells were treated with 0.1-10.0 mM of carnosine or β-alanine for 4, 24 and 72 h. Gene expression was measured at 4 h using real-time quantitative polymerase chain reaction, and amino acid and histidine-containing dipeptides (HCD) concentrations were analyzed at all-time points using an amino acid analyzer. In Study 2, post-mortem human heart ventricle samples (n = 16) were analyzed for carnosine and β-alanine using HPLC-ESI +-MS/MS, and metabolism-related proteins using western blots. H9c2 cardiomyocytes expressed genes related to carnosine and β-alanine metabolism, except for the β-alanine transaminase, AGXT2. Carnosine supplementation did not affect gene expression, whereas β-alanine decreased transporter TAUT and PHT1 expression. Both exogenously supplied carnosine and β-alanine were taken up and accumulated in cardiomyocytes. Carnosine- and β-alanine-related enzymes and transporters are present in human heart ventricles. In conclusion, cardiomyocytes and the human heart express enzymes and transporters required to uptake β-alanine and synthesize carnosine.
MeSH
Genes, Carnosine, Alanine, Amino Acids, Heart, Myocardium, Enzymes, Heart Ventricles, Tissues, Myocytes, Cardiac, Taurine