Brain-derived Neurotrophic Factor Suppresses Tunicamycin-induced Upregulation of Chop in Neurons.
From: Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, Morgantown, West Virginia 26506, USA.
Journal of neuroscience research
- Publish Date: Jun 2007
- ISSN: 0360-4012
- Volume: 85
- Issue: 8
- Pages: 1674-84
- Medium: Print
- Language: English
- Citation (JAMA): Chen Gang, Fan Zhiqin, Wang Xin, et al. Brain-derived Neurotrophic Factor Suppresses Tunicamycin-induced Upregulation of Chop in Neurons.. J. Neurosci. Res. Jun 2007;85:1674-84
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.
Mesh Headings (Keywords): Animals, Brain-Derived Neurotrophic Factor, Cell Death, Cell Nucleus, Cells, Cultured, Endoplasmic Reticulum, Humans, Mice, Neurons, Protein Transport, Rats, Transcription Factor CHOP, Tunicamycin, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17455323
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.