Dynamic effect of heat shock pretreatment on apoptotic responses to TNF-alpha in liver cells. Academic Article uri icon

abstract

  • 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-alpha (TNF-alpha) stimulation. However, vector-mediated overexpression of HSP70 failed to provide similar protection but rather sensitized cells to TNF-alpha 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 TNF-alpha 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 TNF-alpha after HS. Hepatoma cells were subjected to mild heat shock at 42 degrees C for 2 h followed by varied recovery times and then treated with TNF-alpha 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 TNF-alpha induced apoptosis. In addition, we found a window extending up to 2 h after HS where HS sensitized cells to TNF-alpha stress. Importantly, the correlation between apoptosis and HSP expression kinetics demonstrates that both high levels of HSPs and proper timing between HS and TNF-alpha 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.

published proceedings

  • J Biomech Eng

altmetric score

  • 0.25

author list (cited authors)

  • Wang, S., Chen, P. C., Berthiaume, F., Toner, M., Jayaraman, A., & Yarmush, M. L.

citation count

  • 1

complete list of authors

  • Wang, Sihong||Chen, Pohun C||Berthiaume, Francois||Toner, Mehmet||Jayaraman, Arul||Yarmush, Martin L

publication date

  • July 2009