Calcineurin is involved in cardioprotection induced by ischemic postconditioning through attenuating endoplasmic reticulum stress

Chin Med J (Engl). 2011 Oct;124(20):3334-40.

Abstract

Background: Ischemic postconditioning (I-postC) is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion (I/R) injury. Endoplasmic reticulum (ER) is a principal site for secretary protein synthesis and calcium storage. Myocardial I/R causes ER stress and emerging studies suggest that the cardioprotection has been linked to the modulation of ER stress. The aim of the present study was to determine whether cardioprotection of I-postC involves reduction in ER stress through calcineurin pathway.

Methods: In the in vivo model of rat myocardial I/R, myocardial infarct size was measured by triphenyltetrazolium chloride (TTC) staining and apoptosis was detected using terminal eoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Expression of calreticulin, C/EBP homologous protein (CHOP), caspase-12, and activation of caspase-12 in myocardium were detected by Western blotting. The activity and expression of calcineurin in myocardium were also detected.

Results: I-postC protected the I/R heart against apoptosis, myocardial infarction, and leakage of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). I-postC suppressed I/R-induced ER stress, as shown by a decrease in the expression of calreticulin and CHOP, and caspase-12 activation. I-postC downregulated calcineurin activation in myocardium subjected to I/R.

Conclusion: I-postC protects myocardium from I/R injury by suppressing ER stress and calcineurin pathways are not associated with the I-postC-induced suppression of ER stress-related apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Blotting, Western
  • Calcineurin / metabolism*
  • Creatine Kinase, MB Form / blood
  • Endoplasmic Reticulum Stress / physiology*
  • Hemodynamics
  • Ischemic Postconditioning*
  • L-Lactate Dehydrogenase / blood
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / metabolism
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / cytology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • L-Lactate Dehydrogenase
  • Creatine Kinase, MB Form
  • Calcineurin