Document Detail


Volatile anesthetic post-treatment induces protection via inhibition of glycogen synthase kinase 3β in human neuron-like cells.
MedLine Citation:
PMID:  21277352     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Application of the volatile anesthetic isoflurane during the early phase of reperfusion reduces ischemic heart and brain injury (anesthetic post-conditioning). We hypothesize that inhibition of glycogen synthase kinase 3β (GSK3β), a protein whose activation can lead to cell death, participates in anesthetic post-conditioning-induced neuroprotection. SH-SY5Y cells, a human neuroblastoma cell line, were induced by retinoic acid to differentiate into terminal neuron-like cells. The cells were then subjected to a 1-h oxygen-glucose deprivation (OGD), a condition to simulate ischemia in vitro, and a 20-h simulated reperfusion. Isoflurane, sevoflurane or desflurane, three commonly used volatile anesthetics, were applied for 1 h during the early phase of simulated reperfusion. Cell injury was quantified by lactate dehydrogenase (LDH) release. Phospho-GSK3β at Ser9 and total GSK3β were quantified at 1 or 3 h after the OGD. OGD increased LDH release, suggesting that OGD induced cell injury. Post-treatment with isoflurane, sevoflurane or desflurane reduced this cell injury. This protection was apparent when 2% isoflurane was applied within 1 h after the onset of reperfusion. Isoflurane post-treatment also significantly increased the phosphorylation of GSK3β at Ser9 at 1 h after the OGD. GSK3β inhibitors reduced OGD and simulated reperfusion-induced LDH release. The combination of GSK3β inhibitors and isoflurane post-conditioning did not cause a greater protection than isoflurane post-conditioning alone. These results suggest that volatile anesthetic post-conditioning reduces OGD and simulated reperfusion-induced cell injury. Since phospho-GSK3β at Ser9 decreases GSK3β activity, our results suggest that volatile anesthetic post-conditioning in human neuron-like cells may be mediated by GSK3β inhibition.
Authors:
D Lin; G Li; Z Zuo
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-28
Journal Detail:
Title:  Neuroscience     Volume:  179     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-15     Completed Date:  2011-07-13     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  73-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Inhalation / pharmacology*
Blotting, Western
Cell Line
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors*,  metabolism
Humans
Ischemic Postconditioning / methods*
Isoflurane / analogs & derivatives,  pharmacology
Methyl Ethers / pharmacology
Neurons / drug effects*,  enzymology*
Neuroprotective Agents / pharmacology
Grant Support
ID/Acronym/Agency:
R01 GM065211/GM/NIGMS NIH HHS; R01 GM065211/GM/NIGMS NIH HHS; R01 GM065211-07S1/GM/NIGMS NIH HHS; R01 GM065211-08/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Enzyme Inhibitors; 0/Methyl Ethers; 0/Neuroprotective Agents; 28523-86-6/sevoflurane; 57041-67-5/desflurane; CYS9AKD70P/Isoflurane; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections

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