Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells.
10.3858/emm.2009.41.6.049
- Author:
Yoon Mi CHO
1
;
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
Author Information
1. Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. ojkwon@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
bone marrow;
cell differentiation;
embryonic stem cells;
endoplasmic reticulum;
neuron;
stem cells;
stress, physiological;
stromal cells
- MeSH:
Activating Transcription Factor 4/genetics/metabolism;
Animals;
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;
Mice;
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;
Rats;
Stromal Cells
- From:Experimental & Molecular Medicine
2009;41(6):440-452
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
