Apelin protects sarcoplasmic reticulum function and cardiac performance in ischaemia-reperfusion by attenuating oxidation of sarcoplasmic reticulum Ca2+-ATPase and ryanodine receptor

Cardiovasc Res. 2013 Oct 1;100(1):114-24. doi: 10.1093/cvr/cvt160. Epub 2013 Jun 13.

Abstract

Aims: Apelin, an endogenous cytokine, has a number of biological effects on the cardiovascular system, including a cardioprotective effect and calcium modulation. Because the intracellular calcium abnormality is considered to play an important role in cardiac dysfunction induced by ischaemia-reperfusion (I/R), the aim of this study was to examine the effects of apelin-13 on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function.

Methods and results: Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of apelin-13 and inhibitors of some survival kinases. We found that depressed cardiac performance induced by I/R was attenuated by apelin-13. Furthermore, apelin-13 depressed oxidative stress during I/R. SR function depressed during I/R was partly reversed by apelin-13. SR oxidative modification levels were increased in I/R and reversed by apelin. Inhibitors of phosphatidylinositol-3-kinase and protein kinase C abolished the effects of apelin. Apelin-13 maintained the Ca(2+) transient against I/R in cardiomyocytes.

Conclusion: Apelin protects SR function and cardiac performance during I/R by attenuating oxidation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and RyR.

Keywords: Ca2+; Ischaemic contracture; PI3K; PKC; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apelin
  • Calcium / metabolism
  • Glutathione / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / physiology*
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Myocardial Contraction*
  • Myocardial Reperfusion*
  • Oxidation-Reduction
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sarcoplasmic Reticulum / physiology*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
  • Signal Transduction

Substances

  • Apelin
  • Apln protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Reactive Oxygen Species
  • Ryanodine Receptor Calcium Release Channel
  • apelin-13 peptide
  • L-Lactate Dehydrogenase
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Glutathione
  • Calcium