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Ionizing radiation activates PERK/eIF2α/ATF4 signaling via ER stress-independent pathway in human vascular endothelial cells.
MedLine Citation:
PMID:  24456547     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstracts Purpose: Perturbations in protein folding induce endoplasmic reticulum (ER) stress, which elicits coordinated response, namely the unfolded protein response (UPR), to cope with the accumulation of misfolded proteins in ER. In this study, we characterized mechanisms underlying ionizing radiation (IR)-induced UPR signaling pathways. Materials and methods: We analyzed alterations in UPR signaling pathways in human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) irradiated with 15 Gy IR. Results: IR selectively activated the eIF2α/ATF4 branch of the UPR signaling pathway, with no alterations in the IRE1 and ATF6 branches in HUVECs and HCAECs. Phosphorylation of PERK was enhanced in response to IR, and the IR-induced activation of the eIF2α/ATF4 signaling pathway was completely inhibited by PERK knockdown with siRNA. Surprisingly, chemical chaperones, which inhibit the formation of misfolded proteins and sequential protein aggregates to reduce ER stress, failed to prevent the IR-induced phosphorylation of PERK and the subsequent activation of the eIF2α/ATF4 signaling pathway. Conclusions: PERK mediates the IR-induced selective activation of the eIF2α/ATF4 signaling pathway, and the IR-induced activation of PERK/eIF2α/ATF4 signaling in human vascular endothelial cells is independent of alterations in protein-folding homeostasis in the ER.
Authors:
Eun Ju Kim; Yoon-Jin Lee; Seongman Kang; Young-Bin Lim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-24
Journal Detail:
Title:  International journal of radiation biology     Volume:  -     ISSN:  1362-3095     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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