Ischemia-reperfusion, heat shock proteins

Heat shock proteins (HSPs) are synthesized by cells in response to an increase in temperature, as well to various other stressful stimuli. Their main function is to ensure intracellular protein homeostasis, thus preserving the cells viability in the presence of aggression. Current evidence points to a protective role for HSPs in several aspects of critical disease, such as ischemia-reperfusion, ARDS, and multiple organ failure. The increase of a few degrees Celsius above the normal environmental temperature of cells leads to the heat shock response 1) rapid expression of heat shock genes, 2) suppression of normal protein synthesis, and 3) the ability of cells to survive a second and otherwise lethal heat challenge (thermotolerance). 

K. Suzuki, Y. Sawa, Y. Kaneda, H. Ichikawa, R. Shirakura, and H. Matsuda, In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat, J. Clin. Invest. 99 1645 (1997). 

Heat shock proteins is a family of proteins which were identified in relation to heat stress response and they are categorized on the basis of their approximate molecular weights. Heat shock protein induction is a rapid response to altered redox state and closely corresponds to the activity of antioxidant enzymes such as catalase. Heat shock proteins are induced in response to a number of stresses, including sublethal heal, hypoxia, reoxygenation and ischemia and reperfusion. 

Figure 24. Heat shock proteins constitute an endogenous defense system antagonizing protein unfolding or misfolding that occurs upon stress. They enhance cytoskeletal stabili ly, inhibit apoptosis and increase NO synthesis. Ovcrexpcssion of heat shock proteins increases cellular tolerance to ischemia and reperfusion injury.

Delivery of gene transfer systems of heat shock proteins (Hsp70),250 antioxidant enzymes (catalase)251 or survival genes (Akt)252 has been associated with myocardial protection against ischemia and reperfusion. A vector gene therapy system has also been developed with a hypoxia response element-incorporated promoter to turn on the gene expression in response to hypoxic signal.253... 

S. Okubo, O. Wildner, M.R. Shah, J.C. Chelliah, M.L. Hess and R.C. Kukreja, Gene transfer of heat-shock protein 70 reduces infarct size in vivo after ischemia/reperfusion in the rabbit heart, Circulation. 103(6), 877-881 (2001). 

T. Shinohara, N. Takahashi, T. Ooie, M. Ishinose, M. Hara, H. Yoncmoshi, T. Saikawa and H. Yoshimat-su, Estrogen inhibits hyperthermia -induced expression of heat shock protein 72 and cardioprotection against ischemia/reperfusion injury in female rat heart, J. Mol. Cell. Cardiol. 37, 1053-1061 (2004). 

Jayakumar, J., Suzuki, K., Khan, M., Smolenski, R. T., Farrell, A., Latif, N., Raisky, O., Abunasra, H., Sammut, 1. A., Murtuza, B., Amrani, M., and Yacoub, M. H. 2000. Gene therapy for myocardial protection—Transfection of donor hearts with heat shock protein 70 gene protects cardiac function against ischemia - reperfusion injury. Circulation, 102, 302-306. 

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