Document Detail

Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells.
MedLine Citation:
PMID:  19322020     Owner:  NLM     Status:  MEDLINE    
When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2alpha phosphorylation. Transcription of two downstream targets of eIF2alpha, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuronal differentiation of mouse embryonic stem (mES) cells. Finally, chemical endoplasmic reticulum (ER) stress inducers, thapsigargin, tunicamycin, and brefeldin A, dose-dependently increased both mRNA and protein expressions of NF-L, and, its expression was specific to BIP-positive rBMSCs. Our results showing the induction of UPR during neuronal differentiations of rBMSCs and mES cells as well as NF-L expression by ER stress inducers strongly suggest the potential role of UPR in neuronal differentiation.
Yoon Mi Cho; Yoon Seong Jang; Young Min Jang; Sang Mi Chung; Ho Shik Kim; Jeong Hwa Lee; Seong Whan Jeong; In Kyung Kim; Jung Jin Kim; Kwang Soo Kim; Oh Joo Kwon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental & molecular medicine     Volume:  41     ISSN:  1226-3613     ISO Abbreviation:  Exp. Mol. Med.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-07-23     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9607880     Medline TA:  Exp Mol Med     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  440-52     Citation Subset:  IM    
Department of Biochemistry, 2MRC for Cell Death Disease Research Center, Korea.
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MeSH Terms
Activating Transcription Factor 4 / genetics,  metabolism
Apoptosis / drug effects
Bone Marrow Cells / cytology*
Cell Differentiation
Culture Media / pharmacology
Embryonic Stem Cells / cytology*
Endoplasmic Reticulum / genetics,  metabolism
Gene Expression / drug effects
Heat-Shock Proteins / genetics*,  metabolism
Microtubule-Associated Proteins / genetics,  metabolism
Molecular Chaperones / genetics*,  metabolism
Nerve Tissue Proteins / genetics,  metabolism*
Neurofilament Proteins / genetics,  metabolism
Neurons / cytology*
Nuclear Proteins / genetics,  metabolism
Protein Folding
Stromal Cells
Reg. No./Substance:
0/Atf4 protein, rat; 0/Culture Media; 0/Heat-Shock Proteins; 0/Hspa5 protein, rat; 0/Microtubule-Associated Proteins; 0/Molecular Chaperones; 0/Mtap2 protein, rat; 0/Nerve Tissue Proteins; 0/NeuN protein, mouse; 0/Neurofilament Proteins; 0/Nuclear Proteins; 145891-90-3/Activating Transcription Factor 4

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