Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM.

FEBS Open Bio 2014 17;4:813-21. Epub 2014 Sep 17.

Apoptosis Research Centre, NUI Galway, Ireland.

A mild heat shock (HS) preconditioning and acquisition of thermotolerance protects cells against a variety of cytotoxic agents that otherwise induce apoptosis. Here we tested whether there is a molecular link between HS preconditioning and endoplasmic reticulum (ER) stress-induced apoptosis. ER stress results from a loss of ER lumen homeostasis, culminating in an accumulation of unfolded/misfolded proteins in the ER and activation of unfolded protein response (UPR). Unresolved, ER stress leads to activation of BH3-only proteins, mitochondrial membrane permeabilization, caspase activation and apoptotic cell death. HS preconditioning (1 h at 42 °C) induced a rapid increase in HSPA1 (HSP70) levels which remained elevated for at least 48 h post-HS. HS preconditioning significantly reduced BAX, caspase activation and apoptosis in cell cultures treated with the ER stress-inducing agents thapsigargin (TG) and tunicamycin (TM). HS-mediated protection was found to be due to regulation of the BH3-only protein BIM. Further, overexpression of HSPA1 could not mimic the effect of HS on BIM expression, suggesting that other HS factors may play a role in inhibiting ER stress-induced apoptosis by regulating BIM.

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Source
http://doi.wiley.com/10.1016/j.fob.2014.09.004
Publisher Site
http://dx.doi.org/10.1016/j.fob.2014.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208087PMC
October 2014
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