Neurotoxicity Research

, Volume 24, Issue 4, pp 472–477 | Cite as

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy

  • Haiping Wang
  • Kimberly A. Bower
  • Jacqueline A. Frank
  • Mei Xu
  • Jia Luo
Original Article


Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1 % oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al. Free Radic Biol Med 49: 839–846, 2010). We, therefore, hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1 % oxygen) for 8 h significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 h) was 49 ± 6 % of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7 % of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways.


Alcohol Fetal alcohol spectrum disorders Protein degradation Neurodegeneration 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Haiping Wang
    • 1
  • Kimberly A. Bower
    • 1
  • Jacqueline A. Frank
    • 1
  • Mei Xu
    • 1
  • Jia Luo
    • 1
  1. 1.Department of Molecular and Biochemical PharmacologyUniversity of Kentucky College of MedicineLexingtonUSA

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