PMID- 25349785 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20141028 LR - 20181113 IS - 2211-5463 (Print) IS - 2211-5463 (Electronic) IS - 2211-5463 (Linking) VI - 4 DP - 2014 TI - Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM. PG - 813-21 LID - 10.1016/j.fob.2014.09.004 [doi] AB - 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 degrees 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. FAU - Kennedy, Donna AU - Kennedy D AD - Apoptosis Research Centre, NUI Galway, Ireland. FAU - Mnich, Katarzyna AU - Mnich K AD - Apoptosis Research Centre, NUI Galway, Ireland. FAU - Samali, Afshin AU - Samali A AD - Apoptosis Research Centre, NUI Galway, Ireland. LA - eng PT - Journal Article DEP - 20140917 PL - England TA - FEBS Open Bio JT - FEBS open bio JID - 101580716 PMC - PMC4208087 OTO - NOTNLM OT - Apoptosis OT - BCL-2 family OT - BIM OT - ER, endoplasmic reticulum OT - Endoplasmic reticulum stress OT - HS, heat shock OT - Heat shock OT - TG, thapsigargin OT - TM, tunicamycin OT - UPR, unfolded protein response OT - Unfolded protein response EDAT- 2014/10/29 06:00 MHDA- 2014/10/29 06:01 PMCR- 2014/09/17 CRDT- 2014/10/29 06:00 PHST- 2014/06/10 00:00 [received] PHST- 2014/08/11 00:00 [revised] PHST- 2014/09/10 00:00 [accepted] PHST- 2014/10/29 06:00 [entrez] PHST- 2014/10/29 06:00 [pubmed] PHST- 2014/10/29 06:01 [medline] PHST- 2014/09/17 00:00 [pmc-release] AID - S2211-5463(14)00086-2 [pii] AID - 10.1016/j.fob.2014.09.004 [doi] PST - epublish SO - FEBS Open Bio. 2014 Sep 17;4:813-21. doi: 10.1016/j.fob.2014.09.004. eCollection 2014.