Journal article
Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy
Neurotoxicity research, Vol.24(4), pp.472-477
04/09/2013
DOI: 10.1007/s12640-013-9390-7
PMCID: PMC3739993
PMID: 23568540
Abstract
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.
Details
- Title: Subtitle
- Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: The Involvement of Autophagy
- Creators
- Haiping Wang - University of KentuckyKimberly A Bower - University of KentuckyJacqueline A Frank - University of KentuckyMei Xu - University of KentuckyJia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Neurotoxicity research, Vol.24(4), pp.472-477
- DOI
- 10.1007/s12640-013-9390-7
- PMID
- 23568540
- PMCID
- PMC3739993
- NLM abbreviation
- Neurotox Res
- ISSN
- 1029-8428
- eISSN
- 1476-3524
- Publisher
- Springer US
- Language
- English
- Date published
- 04/09/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984201114402771
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