期刊
FEBS OPEN BIO
卷 4, 期 -, 页码 813-821出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.fob.2014.09.004
关键词
Apoptosis; BCL-2 family; BIM; Endoplasmic reticulum stress; Heat shock; Unfolded protein response
资金
- College of Science of NUI Galway
- Science foundation Ireland [09/RFP/BIC2371, 09/RFP/BMT2153]
- Belgian grant - Interuniversity Attraction Poles [IAP 7/32]
- Science Foundation Ireland (SFI) [09/RFP/BIC2371, 09/RFP/BMT2153] Funding Source: Science Foundation Ireland (SFI)
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. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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