Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cells.
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].


CONCLUSIONS
Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption.
Wu
G-J
GJ
Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chen
W-F
WF
Sung
C-S
CS
Jean
Y-H
YH
Hung
C-H
CH
Chen
F-A
FA
Hsieh
M-H
MH
Wen
Z-H
ZH
D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004399:Dynorphins / Q000633:toxicity*; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D004399:Dynorphins; D007530:Isoflurane