Journal article
Ethanol Promotes Endoplasmic Reticulum Stress-Induced Neuronal Death: Involvement of Oxidative Stress
Journal of neuroscience research, Vol.86(4), pp.937-946
03/2008
DOI: 10.1002/jnr.21540
PMCID: PMC3097119
PMID: 17941056
Abstract
One of the most devastating effects of ethanol exposure during development is the loss of neurons in selected brain areas. The underlying cellular/molecular mechanisms remain unclear. The endoplasmic reticulum (ER) is involved in posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress, which is characterized by translational attenuation, synthesis of ER chaperone proteins such as GRP78, and activation of transcription factors such as ATF4, ATF6, and CHOP. Sustained ER stress ultimately leads to cell death. ER stress response can be induced experimentally by treatment with tunicamycin and thapsigargin. Using SH-SY5Y neuroblastoma cells and primary cerebellar granule neurons as in vitro models, we demonstrated that exposure to ethanol alone had little effect on the expression of markers for ER stress; however, ethanol drastically enhanced the expression of GRP78, CHOP, ATF4, ATF6, and phosphorylated PERK and elF2α when induced by tunicamycin and thapsigargin. Consistently, ethanol promoted tunicamycin- and thapsigargin-induced cell death. Ethanol rapidly caused oxidative stress in cultured neuronal cells; antioxidants blocked ethanol’s potentiation of ER stress and cell death, suggesting that the ethanol-promoted ER stress response is mediated by oxidative stress. CHOP is a proapoptotic transcription factor. We further demonstrated that CHOP played an important role in ethanol-promoted cell death. Thus, the effect of ethanol may be mediated by the interaction between oxidative stress and ER stress.
Details
- Title: Subtitle
- Ethanol Promotes Endoplasmic Reticulum Stress-Induced Neuronal Death: Involvement of Oxidative Stress
- Creators
- Gang Chen - West Virginia UniversityCuiling Ma - West Virginia UniversityKimberly A Bower - West Virginia UniversityXianglin Shi - Chinese Academy of SciencesZunji Ke - Chinese Academy of SciencesJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience research, Vol.86(4), pp.937-946
- DOI
- 10.1002/jnr.21540
- PMID
- 17941056
- PMCID
- PMC3097119
- NLM abbreviation
- J Neurosci Res
- ISSN
- 0360-4012
- eISSN
- 1097-4547
- Grant note
- R01 AA015407-03 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 03/2008
- Academic Unit
- Pathology
- Record Identifier
- 9984186494902771
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