Expression of calcineurin, calpastatin and heat shock proteins during ischemia and reperfusion

Sreejit Parameswaran1, Rajendra K Sharma1

  • 1Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5.

Abstract

Insights

Calcineurin (CaN) and calpains (Calp) signaling in cardiomyocytes is modulated by heat shock proteins (Hsp70, Hsp90). These proteins play a significant role in cardio protection during ischemia and reperfusion, influencing cell death and repair mechanisms.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Molecular Medicine

Background:

  • Calcineurin (CaN) and calpains (Calpn) signaling pathways are implicated in cardiomyocyte damage and cell death.
  • Calpastatin (Calp) inhibits calpains and, with CaN stimulation, may promote cell survival and repair.
  • Molecular chaperones, specifically heat shock proteins (Hsp70 and Hsp90), regulate calpain signaling.

Purpose of the Study:

  • To investigate the roles of CaN, Calp, Hsp70, and Hsp90 in murine cardiomyocyte cultures subjected to induced ischemia and reperfusion.
  • To elucidate the interactions between these proteins and their impact on cell viability and death during ischemic events.

Main Methods:

  • Primary murine cardiomyocyte cultures were subjected to induced ischemia and reperfusion.
  • Protein expression levels of CaN, Calp, Hsp70, and Hsp90 were analyzed.
  • Cell viability was assessed using flow cytometry (FACS).

Main Results:

  • Hsp70 and Hsp90 expression increased during ischemia, correlating with increased cell death.
  • Relative expression of Hsp70/Hsp90 to CaN was higher than to Calp during ischemia.
  • Reperfusion led to a decrease in chaperone-expressing cells, reduced CaN expression and cell death, and increased Calp expression with decreased cell death.

Conclusions:

  • Hsp70, Hsp90, CaN, and Calp interact and are crucial for cardio protection.
  • These proteins collectively influence cardiomyocyte survival and death during ischemic and reperfusion injury.

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