Journal article
Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta
Neurotoxicity research, Vol.15(4), pp.321-331
05/2009
DOI: 10.1007/s12640-009-9036-y
PMCID: PMC3093707
PMID: 19384566
Abstract
Ethanol is a potent teratogen for the developing central nervous system (CNS), and fetal alcohol syndrome (FAS) is the most common nonhereditary cause of mental retardation. Ethanol disrupts neuronal differentiation and maturation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Using an in vitro neuronal model, mouse Neuro2a (N2a) neuroblastoma cells, we demonstrated that ethanol inhibited neurite outgrowth and the expression of neurofilament (NF) proteins. Glycogen synthase kinase 3
β
(GSK3
β
), a multi-functional serine/threonine kinase negatively regulated neurite outgrowth of N2a cells; inhibiting GSK3
β
activity by retinoic acid (RA) and lithium induced neurite outgrowth, while over-expression of a constitutively active S9A GSK3
β
mutant prevented neurite outgrowth. Ethanol inhibited neurite outgrowth by activating GSK3
β
through the dephosphorylation of GSK3
β
at serine 9. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family rich in many edible berries and other pigmented fruits, enhanced neurite outgrowth by promoting p-GSK3
β
(Ser9). More importantly, C3G reversed ethanol-mediated activation of GSK3
β
and inhibition of neurite outgrowth as well as the expression of NF proteins. C3G also blocked ethanol-induced intracellular accumulation of reactive oxygen species (ROS). However, the antioxidant effect of C3G appeared minimally involved in its protection. Our study provides a potential avenue for preventing or ameliorating ethanol-induced damage to the developing CNS.
Details
- Title: Subtitle
- Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta
- Creators
- Gang Chen - University of KentuckyKimberly A Bower - University of KentuckyMei Xu - University of KentuckyMin Ding - National Institute for Occupational Safety and HealthXianglin Shi - University of KentuckyZun-Ji Ke - Shanghai Institutes for Biological SciencesJia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Neurotoxicity research, Vol.15(4), pp.321-331
- DOI
- 10.1007/s12640-009-9036-y
- PMID
- 19384566
- PMCID
- PMC3093707
- NLM abbreviation
- Neurotox Res
- ISSN
- 1029-8428
- eISSN
- 1476-3524
- Grant note
- R01 AA015407-03 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 05/2009
- Academic Unit
- Pathology
- Record Identifier
- 9984186522802771
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