Constitutive HSC70 in Ischemia/Reperfusion Protection

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Reactive oxygen species (ROS) are excessively formed during the early stage of reoxygenation of the ischemic heart. These oxygen byproducts may initiate a cascade of damages in membrane integrity, calcium sequestration, and energy homeostasis. The inability of the myocardium to defend itself against the toxic effect of ROS leads to ischemia/reperfusion (I/R) injury. Therefore, modulation of cellular oxidative defenses has a clinical significance with respect to the preservation of ischemic tissues during reperfusion. There exists in cells a unique set of beneficial proteins, the heat shock proteins (hsps). The inducible 70-kD hsp (hsp70) has been demonstrated to have a cardioprotective effect during I/R episodes. Using a simple myocardial model in vitro, H9c2 rat heart-derived myoblasts, we recently found that its constitutive counterpart (hsc70) is also cytoprotective against ROS toxicity. Furthermore, hsc70 has a lower threshold for induction, and thus is suitable for pharmacological manipulation. Our preliminary data show that hsc70 overexpression in cells attenuates lipid peroxidation induced by hydrogen peroxide (H2O2), and that a simultaneous increase in hsc70 and hsp70 confers a greater thermal protection than individual protein alone. Based upon our data, we postulate a hypothesis that hsc70 alone can protect against oxidative and I/R injury, and by its interaction with hsp70, this protein delivers a marked oxidative or I/R resistance. To vigorously test this hypothesis, both H9c2 cell and animal models will be employed. We will examine (1) whether lipid protection is a contributing factor to the antioxidative effect of hsc70; (2) whether hsc70 overexpression alone confers upon the heart and skeletal muscle I/R protection; and (3) the potential interaction between hsc70/hsp70 to improve survival during oxidative or I/R challenge. This study should improve our understanding of the protective potency and mechanism(s) of hsc70, and moreover it will prove feasibility for using hsc70 protein in the treatment of I/R injury.

Project IDs

Project ID:PC9706-0161
External Project ID:NSC95-2320-B182-028-MY3
Effective start/end date01/08/0831/07/09


  • HSP70
  • HSC70
  • cytoprotection
  • oxidative stress
  • Ischemia/reperfusion


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