Journal article
Brain-Derived Neurotrophic Factor Suppresses Tunicamycin-Induced Upregulation of CHOP in Neurons
Journal of neuroscience research, Vol.85(8), pp.1674-1684
06/2007
DOI: 10.1002/jnr.21292
PMCID: PMC3085896
PMID: 17455323
Abstract
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen triggers ER stress. ER stress initiates a number of specific compensatory signaling pathways including unfolded protein response (UPR). UPR is characterized by translational attenuation, synthesis of ER chaperone proteins such as glucose-regulated protein of 78 kDa (GRP78, also known as Bip), and transcriptional induction, which includes the activation of transcription factors such as activating transcriptional factor 6 (ATF6) and C/EBP homologous protein (CHOP, also known as growth arrest and DNA damage-inducible gene 153 [GADD153]). Sustained ER stress ultimately leads to cell death. ER functions are believed to be impaired in various neurodegenerative diseases, as well as in some acute disorders of the brain. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, functions as a neuroprotective agent and rescues neurons from various insults. The molecular mechanisms underlying BDNF neuroprotection, however, remain to be elucidated. We showed that CHOP partially mediated ER stress-induced neuronal death. BDNF suppressed ER stress-induced upregulation/nuclear translocation of CHOP. The transcription of CHOP is regulated by ATF4, ATF6, and XBP1; BDNF selectively blocked the ATF6/CHOP pathway. Furthermore, BDNF inhibited the induction of death receptor 5 (DR5), a transcriptional target of CHOP. Our study thus suggests that suppression of CHOP activation may contribute to BDNF-mediated neuroprotection during ER stress responses.
Details
- Title: Subtitle
- Brain-Derived Neurotrophic Factor Suppresses Tunicamycin-Induced Upregulation of CHOP in Neurons
- Creators
- Gang Chen - West Virginia UniversityZhiqin Fan - Chinese Academy of SciencesXin Wang - Chinese Academy of SciencesCuiling Ma - West Virginia UniversityKimberly A Bower - West Virginia UniversityXianglin Shi - Chinese Academy of SciencesZun-Ji Ke - Shanghai Institutes for Biological SciencesJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience research, Vol.85(8), pp.1674-1684
- DOI
- 10.1002/jnr.21292
- PMID
- 17455323
- PMCID
- PMC3085896
- ISSN
- 0360-4012
- eISSN
- 1097-4547
- Grant note
- R01 AA015407-03 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 06/2007
- Academic Unit
- Pathology
- Record Identifier
- 9984186411302771
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