nach oben

Neurotoxicity Research

Erschienen in:

01.05.2009

Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta

verfasst von: Gang Chen, Kimberly A. Bower, Mei Xu, Min Ding, Xianglin Shi, Zun-Ji Ke, Jia Luo

Erschienen in: Neurotoxicity Research | Ausgabe 4/2009

Einloggen, um Zugang zu erhalten

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 3β (GSK3β), a multifunctional serine/threonine kinase negatively regulated neurite outgrowth of N2a cells; inhibiting GSK3β activity by retinoic acid (RA) and lithium induced neurite outgrowth, while over-expression of a constitutively active S9A GSK3β mutant prevented neurite outgrowth. Ethanol inhibited neurite outgrowth by activating GSK3β through the dephosphorylation of GSK3β 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-GSK3β(Ser9). More importantly, C3G reversed ethanol-mediated activation of GSK3β 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.

Abel EL (1984) Prenatal effects of alcohol. Drug Alcohol Depend 14:1–10PubMedCrossRef

Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA (2005) Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8:111–120PubMedCrossRef

Bagchi D, Sen CK, Bagchi M, Atalay M (2004) Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry (Mosc) 69:75–80CrossRef

Chakraborty G, Saito M, Mao RF, Wang R, Vadasz C, Saito M (2008) Lithium blocks ethanol-induced modulation of protein kinases in the developing brain. Biochem Biophys Res Commun 367:597–602PubMedCrossRef

Chen G, Bower KA, Ma C, Fang S, Thiele CJ, Luo J (2004) Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death. FASEB J 18:1162–1164PubMedCrossRef

Chen G, Ma C, Bower KA, Shi X, Ke Z, Luo J (2008) Ethanol promotes endoplasmic reticulum stress-induced neuronal death: involvement of oxidative stress. J Neurosci Res 86:937–946PubMedCrossRef

Dasgupta B, Milbrandt J (2007) Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci U S A 104:7217–7222PubMedCrossRef

De Girolamo LA, Billett EE, Hargreaves AJ (2000) Effects of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine on differentiating mouse N2a neuroblastoma cells. J Neurochem 75:133–140PubMedCrossRef

de la Monte SM, Wands JR (2002) Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons. Cell Mol Life Sci 59:882–893CrossRef

Diamond I, Gordon AS (1997) Cellular and molecular neuroscience of alcoholism. Physiol Rev 77:1–20PubMed

Ding M, Feng R, Wang SY, Bowman L, Lu Y, Qian Y, Castranova V, Jiang BH, Shi X (2006) Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem 281:17359–17368PubMedCrossRef

Ebrahim SH, Diekman ST, Floyd RL, Decoufle P (1999) Comparison of binge drinking among pregnant and nonpregnant women, United States, 1991–1995. Am J Obstet Gynecol 180:1–7PubMedCrossRef

Galli RL, Shukitt-Hale B, Youdim KA, Joseph JA (2002) Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann N Y Acad Sci 959:128–132PubMedCrossRef

García-Pérez J, Avila J, Díaz-Nido J (1999) Lithium induces morphological differentiation of mouse neuroblastoma cells. J Neurosci Res 57:261–270PubMedCrossRef

Ghosh D, Konishi T (2007) Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac J Clin Nutr 16:200–208PubMed

Goodlett CR, Horn KH (2001) Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Res Health 25:175–184PubMed

Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65:391–426PubMedCrossRef

Hou DX (2003) Potential mechanisms of cancer chemoprevention by anthocyanins. Curr Mol Med 3:149–159PubMedCrossRef

LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2’, 7’-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231PubMedCrossRef

Lee YI, Seo M, Kim Y, Kim SY, Kang UG, Kim YS, Juhnn YS (2005) Membrane depolarization induces the undulating phosphorylation/dephosphorylation of glycogen synthase kinase 3beta, and this dephosphorylation involves protein phosphatases 2A and 2B in SH-SY5Y human neuroblastoma cells. J Biol Chem 280:22044–22052PubMedCrossRef

Luo J, Miller MW (1998) Growth factor-mediated neural proliferation: target of ethanol toxicity. Brain Res Brain Res Rev 27:157–167PubMedCrossRef

Luo J, Lindström CL, Donahue A, Miller MW (2001) Differential effects of ethanol on the expression of cyclo-oxygenase in cultured cortical astrocytes and neurons. J Neurochem 76:1354–1363PubMedCrossRef

Ma C, Wang J, Gao Y, Gao TW, Chen G, Bower KA, Odetallah M, Ding M, Ke Z, Luo J (2007) The role of glycogen synthase kinase 3beta in the transformation of epidermal cells. Cancer Res 67:7756–7764PubMedCrossRef

Mattson SN, Schoenfeld AM, Riley EP (2001) Teratogenic effects of alcohol on brain and behavior. Alcohol Res Health 25:185–191PubMed

May PA, Gossage JP (2001) Estimating the prevalence of fetal alcohol syndrome. Alcohol Res Health 25:159–167PubMed

Muñoz-Montaño JR, Lim F, Moreno FJ, Avila J, Díaz-Nido J (1999) Glycogen synthase kinase-3 modulates neurite outgrowth in cultured neurons: possible implications for neurite pathology in Alzheimer’s Disease. J Alzheimers Dis 1:361–378PubMed

Naska S, Park KJ, Hannigan GE, Dedhar S, Miller FD, Kaplan DR (2006) An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth. J Neurosci 26:13344–13356PubMedCrossRef

O’Callaghan FV, O’Callaghan M, Najman JM, Williams GM, Bor W (2003) Maternal alcohol consumption during pregnancy and physical outcomes up to 5 years of age: a longitudinal study. Early Hum Dev 71:137–148PubMedCrossRef

O’Callaghan FV, O’Callaghan M, Najman JM, Williams GM, Bor W (2007) Prenatal alcohol exposure and attention, learning and intellectual ability at 14 years: a prospective longitudinal study. Early Hum Dev 83:115–123PubMedCrossRef

O’Malley KD, Nanson J (2002) Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder. Can J Psychiatry 47:349–354PubMed

Olney JW (2004) Fetal alcohol syndrome at the cellular level. Addict Biol 9:137–149PubMedCrossRef

Orme MH, Giannini AL, Vivanco MD, Kypta RM (2003) Glycogen synthase kinase-3 and Axin function in a beta-catenin-independent pathway that regulates neurite outgrowth in neuroblastoma cells. Mol Cell Neurosci 24:673–686PubMedCrossRef

Prior RL (2003) Fruits and vegetables in the prevention of cellular oxidative damage. Am J Clin Nutr 78:570S–578SPubMed

Riley EP, McGee CL (2005) Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med (Maywood) 230:357–365

Shin WH, Park SJ, Kim EJ (2006) Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats. Life Sci 79:130–137PubMedCrossRef

Shukitt-Hale B, Carey AN, Jenkins D, Rabin BM, Joseph JA (2007) Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging 28:1187–1194PubMedCrossRef

Shukitt-Hale B, Lau FC, Joseph JA (2008) Berry fruit supplementation and the aging brain. J Agric Food Chem 56:636–641PubMedCrossRef

Stratton K, Howe C, Battagila F (eds) (1996) Fetal alcohol syndrome: diagnosis, epidemiology, prevention, and treatment. National Academy Press, Washington DC

Stromland K, Pinazo-Duran MD (2002) Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol Alcohol 37:2–8PubMed

Sweeney MI, Kalt W, MacKinnon SL, Ashby J, Gottschall-Pass KT (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5:427–431PubMedCrossRef

Takahashi M, Yasutake K, Tomizawa K (1999) Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3beta-dependent phosphorylation of juvenile tau in cultured hippocampal neurons. J Neurochem 73:2073–2083PubMed

Talavéra S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison JL, Rémésy C (2005) Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53:3902–3908PubMedCrossRef

Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D (2007) Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res 51:675–683PubMedCrossRef

Zhang F, Phiel CJ, Spece L, Gurvich N, Klein PS (2003) Inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) in response to lithium. Evidence for autoregulation of GSK-3. J Biol Chem 278:33067–33077PubMedCrossRef

Zhong J, Yang X, Yao W, Lee W (2006) Lithium protects ethanol-induced neuronal apoptosis. Biochem Biophys Res Commun 350:905–910PubMedCrossRef

Titel: Cyanidin-3-Glucoside Reverses Ethanol-Induced Inhibition of Neurite Outgrowth: Role of Glycogen Synthase Kinase 3 Beta
verfasst von: Gang Chen
Kimberly A. Bower
Mei Xu
Min Ding
Xianglin Shi
Zun-Ji Ke
Jia Luo
Publikationsdatum: 01.05.2009
Verlag: Springer-Verlag
Erschienen in: Neurotoxicity Research / Ausgabe 4/2009
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-009-9036-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2009

Non-hypoxic Stabilization of Hypoxia-Inducible Factor Alpha (HIF-α): Relevance in Neural Progenitor/Stem Cells

5-Hydroxyanthranilic Acid, a Tryptophan Metabolite, Generates Oxidative Stress and Neuronal Death via p38 Activation in Cultured Cerebellar Granule Neurones

Neuronal and Glial Alterations Due to Focal Cortical Hypoxia Induced by Direct Cobalt Chloride (CoCl2) Brain Injection

Nicotine Induces Sensitization of Turning Behavior in 6-Hydroxydopamine Lesioned Rats

Neuroprotective Effect of Ghrelin in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson’s Disease by Blocking Microglial Activation

Metallothionein Treatment Attenuates Microglial Activation and Expression of Neurotoxic Quinolinic Acid Following Traumatic Brain Injury