Isoflurane preconditioning protects human neuroblastoma SH-SY5Y cells against in vitro simulated ischemia-reperfusion through the activation of extracellular signal-regulated kinases pathway.
It has been reported that a prior exposure of isoflurane, a commonly used volatile anesthetic in clinical practice, reduces brain cell death after ischemia. This isoflurane preconditioning-induced neuroprotection has been shown in rat in vivo and in vitro brain ischemia models. To investigate the mechanisms of this protection, we used the human neuroblastoma SH-SY5Y cells and simulated ischemia in vitro by oxygen-glucose deprivation. We found that isoflurane exposure for 30 min at 24 h before a 5-h oxygen-glucose deprivation dose-dependently reduced cell death. Isoflurane exposure induced phosphorylation/activation of extracellular signal-regulated kinase (ERK). Inhibition of the phospho-ERK expression abolished the isoflurane preconditioning-induced protection. Isoflurane exposure also increased the expression of early growth response gene 1 (Egr-1) and Bcl-2, proteins downstream of ERK. Egr-1 is a transcription factor and plays a role in cell survival. Bcl-2 is an anti-apoptotic protein. The increased expression of Egr-1 and Bcl-2 by isoflurane was inhibited by ERK inhibition. Thus, our results suggest a role of ERK/Egr-1/Bcl-2 pathway in the isoflurane preconditioning-induced protection in the human neuroblastoma SH-SY5Y cells.
Zuo
Zhiyi
Z
Department of Anesthesiology and Neuroscience, University of Virginia, Charlottesville, VA 22908, USA. zz3c@virginia.edu
Wang
Ying
Y
Huang
Yueming
Y
D002070:Butadienes / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications; D007530:Isoflurane / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects*
D002070:Butadienes; C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C113580:U 0126; D007530:Isoflurane; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose