Document Detail

Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cells.
MedLine Citation:
PMID:  19032555     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: It has been proposed that the volatile anesthetic isoflurane induces neuroprotection and that the endogenous opioid peptide dynorphin induces neurocytotoxicity in cells. The levels of dynorphin are often significantly elevated in neuropathophysiological conditions, and dynorphin can directly induce toxicity. However, the neuroprotective effects of isoflurane on dynorphin-induced cytotoxicity are still unclear. METHODS: In order to determine the effect of isoflurane on dynorphin-induced cytotoxicity in neuronal cells, we have designed a device wherein cultured human neuroblastoma SH-SY5Y cells can be exposed to isoflurane. Fully differentiated SH-SY5Y cells were obtained by treating the cells with retinoic acid for 6 days. We examined SH-SY5Y cell survival, apoptosis, and antiapoptotic protein expression by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain, and Western blot analysis, respectively. RESULTS: After 16 h of dynorphin (10 microM) treatment, the SH-SY5Y cells showed significant cytotoxicity, apoptosis, and downregulation of the antiapoptotic Bcl-2 protein expression. These effects of dynorphin were significantly inhibited by isoflurane exposure for 32 h [pretreatment for 16 h and posttreatment (after dynorphin treatment) for 16 h]. CONCLUSION: Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption.
G-J Wu; W-F Chen; C-S Sung; Y-H Jean; C-H Hung; F-A Chen; M-H Hsieh; Z-H Wen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-11
Journal Detail:
Title:  Acta anaesthesiologica Scandinavica     Volume:  53     ISSN:  1399-6576     ISO Abbreviation:  Acta Anaesthesiol Scand     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-08     Completed Date:  2009-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370270     Medline TA:  Acta Anaesthesiol Scand     Country:  England    
Other Details:
Languages:  eng     Pagination:  55-60     Citation Subset:  IM    
Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
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MeSH Terms
Apoptosis / drug effects
Cell Differentiation*
Cell Line, Tumor
Down-Regulation / drug effects*
Dynorphins / toxicity*
Isoflurane / pharmacology*
Neuroblastoma / metabolism*,  pathology*
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 26675-46-7/Isoflurane; 74913-18-1/Dynorphins

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