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Amino Acids

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Carnosine protects cardiac myocytes against lipid peroxidation products

  • Jingjing Zhao
  • Dheeraj Kumar Posa
  • Vijay Kumar
  • David Hoetker
  • Amit Kumar
  • Smirthy Ganesan
  • Daniel W. Riggs
  • Aruni Bhatnagar
  • Michael F. Wempe
  • Shahid P. Baba
Original Article
  • 134 Downloads
Part of the following topical collections:
  1. Carnosine

Abstract

Endogenous histidyl dipeptides such as carnosine (β-alanine-l-histidine) form conjugates with lipid peroxidation products such as 4-hydroxy-trans-2-nonenal (HNE and acrolein), chelate metals, and protect against myocardial ischemic injury. Nevertheless, it is unclear whether these peptides protect against cardiac injury by directly reacting with lipid peroxidation products. Hence, to examine whether changes in the structure of carnosine could affect its aldehyde reactivity and metal chelating ability, we synthesized methylated analogs of carnosine, balenine (β-alanine-Nτ-methylhistidine) and dimethyl balenine (DMB), and measured their aldehyde reactivity and metal chelating properties. We found that methylation of Nτ residue of imidazole ring (balenine) or trimethylation of carnosine backbone at Nτ residue of imidazole ring and terminal amine group dimethyl balenine (DMB) abolishes the ability of these peptides to react with HNE. Incubation of balenine with acrolein resulted in the formation of single product (m/z 297), whereas DMB did not react with acrolein. In comparison with carnosine, balenine exhibited moderate acrolein quenching capacity. The Fe2+ chelating ability of balenine was higher than that of carnosine, whereas DMB lacked chelating capacity. Pretreatment of cardiac myocytes with carnosine increased the mean lifetime of myocytes superfused with HNE or acrolein compared with balenine or DMB. Collectively, these results suggest that carnosine protects cardiac myocytes against HNE and acrolein toxicity by directly reacting with these aldehydes. This reaction involves both the amino group of β-alanyl residue and the imidazole residue of l-histidine. Methylation of these sites prevents or abolishes the aldehyde reactivity of carnosine, alters its metal-chelating property, and diminishes its ability to prevent electrophilic injury.

Keywords

Acrolein Cardiac myocytes Histidyl dipeptides 4-Hydroxy-trans-2-nonenal 

Notes

Acknowledgements

We would like to thank Bioanalytical Core of the Diabetes and Obesity Center for biochemical analysis.

Funding

This work was supported by grants from the National Institutes of Health, R01HL122581-01 (SPB), R01HL55477 and GM103492 (AB).

Compliance with ethical standards

Conflict of Interest

All authors declare that no competing financial interest exists.

Ethical approval

All treatments and protocols were approved by the University of Louisville, Institutional Animal Care and Use Committee. The ethical approval number is 15387.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Jingjing Zhao
    • 1
    • 2
  • Dheeraj Kumar Posa
    • 1
    • 2
  • Vijay Kumar
    • 3
  • David Hoetker
    • 1
    • 2
  • Amit Kumar
    • 3
  • Smirthy Ganesan
    • 1
    • 2
  • Daniel W. Riggs
    • 1
    • 2
  • Aruni Bhatnagar
    • 1
    • 2
  • Michael F. Wempe
    • 3
  • Shahid P. Baba
    • 1
  1. 1.Department of Medicine, Diabetes and Obesity CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of Medicine, Envirome InstituteUniversity of LouisvilleLouisvilleUSA
  3. 3.Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of ColoradoAuroraUSA

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