Exp Mol Med.
2009 Jun;41(6):440-452. 10.3858/emm.2009.41.6.049.
Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells
- Affiliations
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- 1Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. ojkwon@catholic.ac.kr
- 2MRC for Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
- 3Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
- 4Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
- KMID: 756236
- DOI: http://doi.org/10.3858/emm.2009.41.6.049
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.
Keyword
MeSH Terms
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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
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