The heat shock (HS) response is a protective mechanism for cells to protect themselves against subsequent lethal stress. HS upregulated heat shock protein (HSP) expression reduced apoptosis following tumor necrosis factor- () stimulation. However, vector-mediated overexpression of HSP70 failed to provide similar protection but rather sensitized cells to induced apoptosis. This may be due to the fact that the kinetics of vector-mediated HSP overexpression is totally different from that of HSP upregulation by HS. We hypothesized that the response depends on the timing of challenge relative to HSP expression dynamics after HS. Therefore, we investigated the correlation between the dynamic change of HSP expression and the levels of apoptosis induced by after HS. Hepatoma cells were subjected to mild heat shock at for 2 h followed by varied recovery times and then treated with to induce apoptosis. The results from quantitative apoptosis assays using the TUNEL reaction reveal an optimal HS protection window centered around 5 h post-HS against induced apoptosis. In addition, we found a window extending up to 2 h after HS where HS sensitized cells to stress. Importantly, the correlation between apoptosis and HSP expression kinetics demonstrates that both high levels of HSPs and proper timing between HS and stress were critical for optimal protection. Our study establishes a dynamic experimental model for further investigation of HS as a potential clinical approach to target tissue survival or death.
Dynamic Effect of Heat Shock Pretreatment on Apoptotic Responses to in Liver Cells
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Wang, S., Chen, P. C., Berthiaume, F., Toner, M., Jayaraman, A., and Yarmush, M. L. (June 5, 2009). "Dynamic Effect of Heat Shock Pretreatment on Apoptotic Responses to in Liver Cells." ASME. J Biomech Eng. July 2009; 131(7): 071003. https://doi.org/10.1115/1.3118768
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