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Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway
- Source :
- Brain Research. 1636:13-20
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Isoflurane has either neuroprotective or neurotoxic effects. High-dose oxygen is frequently used throughout the perioperative period. We hypothesized that hyperoxia will affect cell viability of rat pheochromocytoma (PC12) cells that were exposed to isoflurane and reactive oxygen species (ROS) may be involved. PC12 cells were exposed to 1.2% or 2.4% isoflurane for 6 or 24h respectively, and cell viability was evaluated. To investigate the effects of hyperoxia, PC12 cells were treated with 21%, 50%, or 95% oxygen and 2.4% isoflurane for 6h, and cell viability, TUNEL staining, ROS production, and expression of B-cell lymphoma 2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 and beta-site APP cleaving enzyme (BACE) were measured. ROS involvement was evaluated using the ROS scavenger 2-mercaptopropiopylglycine (MPG). The viability of cells exposed to 2.4% isoflurane was lower than that of cells exposed to 1.2% isoflurane. Prolonged exposure (6h vs. 24h) to 2.4% isoflurane resulted in a profound reduction in cell viability. Treatment with 95% (but not 50%) oxygen enhanced the decrease in cell viability induced by 2.4% isoflurane alone. Levels of ROS, Bax, caspase-3 and BACE were increased, whereas expression of Bcl-2 was decreased, in cells treated with 95% oxygen plus 2.4% isoflurane compared with the control and 2.4% isoflurane plus air groups. MPG attenuated the effects of oxygen and isoflurane. In conclusion, isoflurane affects cell viability in a dose- and time-dependent manner. This effect is augmented by hyperoxia and may involve ROS, the mitochondrial apoptotic signaling pathway, and β-amyloid protein.
- Subjects :
- Time Factors
Cell Survival
Apoptosis
Hyperoxia
PC12 Cells
Statistics, Nonparametric
Andrology
03 medical and health sciences
0302 clinical medicine
Bcl-2-associated X protein
030202 anesthesiology
In Situ Nick-End Labeling
medicine
Animals
Viability assay
Molecular Biology
bcl-2-Associated X Protein
chemistry.chemical_classification
Reactive oxygen species
TUNEL assay
Isoflurane
biology
General Neuroscience
Mitochondria
Rats
Proto-Oncogene Proteins c-bcl-2
Biochemistry
chemistry
Anesthetics, Inhalation
biology.protein
Apoptotic signaling pathway
Neurology (clinical)
medicine.symptom
Reactive Oxygen Species
030217 neurology & neurosurgery
Signal Transduction
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1636
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....21f60d5d6abcabb2ce08081689f0599e