Skip to main content

Advertisement

SpringerLink
Log in

l-Glycyl-l-glutamine provides the isolated and perfused young and middle-aged rat heart protection against ischaemia–reperfusion injury

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

The amino acids glycine and glutamine have been implicated in myocardial protection of the much studied young adult heart. This study aimed to determine whether such protection could be enhanced using the dipeptide, l-glycyl-l-glutamine (gly-gln) in both young hearts and in middle-aged hearts representative of a more clinically relevant age group. Hearts from 8-week-old and 36-week-old rats were perfused in the Langendorff mode for 20 min, before 40 min global normothermic ischaemia and 30 min reperfusion. Where present, 0.5, 2, or 5 mM gly-gln was added 10 min into baseline perfusion, was present throughout ischaemia and was washed out after 10 min reperfusion. Reperfusion damage was assessed from the release of lactate dehydrogenase. Metabolic fitness was assessed from the time to ischaemic contracture and the accumulation of lactate and thiobarbituric acid reactive substances during ischaemia. The presence of 5 mM gly-gln significantly improved the post-ischaemic rate pressure product (RPP) and decreased reperfusion damage in both the 8 (RPP in control on reperfusion 5527 ± 957  vs. 10,320 ± 795 mmHg beat min−1 in 5 mM gly-gln, n = 6 ± SE, p < 0.05) and 36-week-old (RPP in control on reperfusion 1964.33 ± 876.3 vs. 4008 ± 675 mmHg beat min−1, n = 6 ± SE, p < 0.01) hearts. Five mM gly-gln also increased the time to ischaemic contracture and was able to protect against the rise in lactate that occurred in the controls during ischaemia. These results suggest that gly-gln has good potential as a combatant against ischaemia–reperfusion injury in both the young adult and middle-aged populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Andreadou I, Iliodromitis EK, Farmakis D, Kremastinos DT (2009) To prevent, protect and save the ischemic heart: antioxidants revisited. Expert Opin Ther Targets 13:945–956

    Article  CAS  PubMed  Google Scholar 

  • Bolotin G, Raman J, Williams U, Bacha E, Kocherginsky M, Jeevanandam V (2007) Glutamine improves myocardial function following ischemia-reperfusion injury. Asian Cardiovasc Thorac Ann 15:463–467

    Article  PubMed  Google Scholar 

  • Broer S (2014) The SLC38 family of sodium-amino acid transporters. Pflügers Arch 466:155–172

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP, Pasdois P (2009) The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta Bioenerg 1787:1402–1415

    Article  CAS  Google Scholar 

  • Jahangir A, Sagar S, Terzic A (2007) Aging and cardioprotection. J Appl Physiol 103:2120–2128

    Article  PubMed  Google Scholar 

  • Jiang L, Qin X, Zhong X, Liu L, Jiang L, Lu Y, Fan L, He Z, Chen Q (2011) Glycine-induced cytoprotection is mediated by ERK1/2 and AKT in renal cells with ATP depletion. Eur J Cell Biol 90:333–341

    Article  CAS  PubMed  Google Scholar 

  • Khogali SE, Harper AA, Lyall JA, Rennie MJ (1998) Effects of l-glutamine on post-ischaemic cardiac function: protection and rescue. J Mol Cell Cardiol 30(4):819–827

    Article  CAS  PubMed  Google Scholar 

  • King N, Lin H, McGivan JD, Suleiman M-S (2004) Aspartate transporter activity in hypertrophic rat heart and ischaemia-reperfusion injury. J Physiol 556:849–858

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • King N, Lin H, McGivan JD, Suleiman M-S (2006) Glutamate transporter activity in hypertrophic rat heart and ischaemia-reperfusion injury. Pflügers Arch 452:674–682

    Article  CAS  PubMed  Google Scholar 

  • King N, Lin H, Suleiman M-S (2011) Oxidative stress increases SNAT1 expression and stimulates cysteine uptake in freshly isolated rat cardiomyocytes. Amino Acids 40:517–526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin H, King N (2007) Demonstration of functional dipeptide uptake into freshly isolated guinea-pig cardiomyocytes. Pflügers Arch 453:915–922

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Marchase RB, Chatham JC (2007) Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. J Mol Cell Cardiol 42:177–185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McGuinness J, Neilan TG, Cummins R, Sharkasi A, Bouchier-Hayes D, Redmond JM (2009) Intravenous glutamine enhances COX-2 activity giving cardioprotection. J Surg Res 152:140–147

    Article  CAS  PubMed  Google Scholar 

  • Nadtochiy SM, Burwell LS, Ingraham CA, Spencer CM, Friedman AE, Pinkert CA, Brookes PS (2009) In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine. J Mol Cell Cardiol 46(6):960–968

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pantos C, Mourouzis I, Cokkinos DV (2007) Protection of the abnormal heart. Heart Fail Rev 12:319–330

    Article  PubMed  Google Scholar 

  • Qi R-B, Xiong Y, Lu D-X, Wang Y-P, Fu Y-M (2009) Protection of glycyl-l-glutamine against myocardial ischemia reperfusion injury in the isolated rat heart. Chin J Pathophysiol 25:853–858

    CAS  Google Scholar 

  • Ruiz-Meana M, Pina P, Garcia-Dorado D, Rodriguez-Sinovas A, Barba I, Miro-Casas E, Mirabet M, Soler-Soler J (2004) Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition. J Physiol 558:873–882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schaffer SW, Jong CJ, Ito T, Azuma J (2014) Effect of taurine on ischemia-reperfusion injury. Amino Acids 46:21–30

    Article  CAS  PubMed  Google Scholar 

  • Shackebaei D, King N, Shukla B, Suleiman M-S (2015) Mechanisms underlying the cardioprotective effects of l-cysteine. Mol Cell Biochem 177:27–31

    Google Scholar 

  • Smith DE, Clemencou B, Hediger MA (2013) Proton-coupled oligopeptide transporter family SLC15: physiological pharmacological and pathological implications. Mol Aspects Med 34:323–336

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Song JX, Tu XH, Wang L, Li CJ (2004) Glutamine dipeptide-supplemented parenteral nutrition in patients with colorectal cancer. Clin Nutr 1:49–53

    CAS  Google Scholar 

  • Støttrup NB, Kristiansen SB, Løfgren B, Hansen BF, Kimose HH, Bøtker HE, Nielsen TT (2006) l-Glutamate and Glutamine improve haemodynamic function and restore myocardial Glycogen content during postischaemic reperfusion: a radioactive tracer study in the rat isolated heart. Clin Exp Pharmacol Physiol 33:1099–1103

    Article  PubMed  Google Scholar 

  • Zhang Y, Yan H, Lv S-G, Wang L, Liang G-P, Wan Q-X, Peng X (2013) Effects of glycyl-l-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury. Int J Clin Exp Pathol 6:821–830

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the University of New England. We would also like to thank the technical staff for their excellent assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. School of Science and Technology, University of New England, Armidale, NSW, 2351, Australia

    Amer Almashhadany, Othman A. Alghamdi, Thomas Van der Touw & Graham L. Jones

  2. School of Biomedical and Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, PL4 8AA, UK

    Nicola King

Authors
  1. Amer Almashhadany
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Othman A. Alghamdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Van der Touw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Graham L. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicola King
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola King.

Additional information

Handling Editor: F. Galli.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Almashhadany, A., Alghamdi, O.A., Van der Touw, T. et al. l-Glycyl-l-glutamine provides the isolated and perfused young and middle-aged rat heart protection against ischaemia–reperfusion injury. Amino Acids 47, 1559–1565 (2015). https://doi.org/10.1007/s00726-015-1997-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-015-1997-y

Keywords

Search

Navigation