pofol on the inhibition of OGD-induced autophagosomes in neuronal PC12 7 purchase Neuromedin N propofol Prevents Autophagic Cell Death cells. The formation of such autophagosomes is essential for autophagic cell death, as demonstrated by the increased numbers of LC3-II-positive neurons and the increased expression of class III PI3K and Beclin-1, which are key proteins in autophagy induction. The prevention of neuron death by the inhibition of autophagy after hypoxic-ischemic injury has been documented to be dependent on an autophagy induction-related gene, Atg7. The present results indicate that a group of factors including class III PI3K, Beclin-1 and Bcl-2 are also engaged in the neuroprotection of propofol against OGD-induced damage in neuronal PC12 cells. The experimental evidence supporting such an argument includes the inhibition of class III PI3KBeclin-1, the formation of autophagosomes, and the increase in the level of Bcl-2 by propofol in vitro. The role of autophagy in neurodegeneration and neuroprotection is elusive. Rapamycin, an autophagy-inducing drug, can provide protection in models of neurodegenerative diseases, which indicates that neurodegeneration is inhibited by autophagy. However, excessive autophagic responses could become hazardous and harmful. Indeed, it has been demonstrated that mutations in lysosomal surface proteins and a variety of deficits in lysosomal Propofol Prevents Autophagic Cell Death enzymes are able to cause prominent neurodegeneration. The results of the present study revealed that the formation of AVs in both OGD-exposed PC12 cells and I/R-injured hippocampal neurons in rats was associated with a reduced number of cells, indicating that autophagy-related processes may promote cell death. This result agrees with those of Li et al, who showed that 
the inhibition of autophagy with lithium reduced brain injury after hypoxia-ischemia in neonatal rats. The present data also indicate that autophagic cell death was 9 Propofol Prevents Autophagic Cell Death regions of the ipsilateral hippocampus 1, 3, 6, 12 and 24 h following I/R. I/R increased the LC3-II-positive cells and LC3-II protein levels in the ischemic hippocampus after I/R in rats. I/R was induced by two-vessel occlusion. Representative photomicrographs of LC3-II immunofluorescence. Immunofluorescence of LC3-II was performed at 024 h after I/R. Images were taken from the same part of the ischemic hippocampus. 24517231” The quantitative analysis of the number of LC3-II-positive cells. The number of LC3-II-positive cells in the ischemic hippocampus was significantly increased in the ischemic rats compared to the sham rats. 8396143 The data are expressed as percentage of the shamoperated animals and as the mean6SD, n = 6. The statistical analysis was performed using a one-way ANOVA. p, 0.05, p, 0.01 vs. sham group. doi:10.1371/journal.pone.0035324.g009 attenuated by propofol, adding a new neuroprotective mechanism for this agent that has not been reported previously. A number of mechanisms have been associated with the neuroprotective effects of propofol, including the reduction in the cerebral metabolic rate of oxygen, the antioxidant-based removal of lipophilic and hydrophilic radicals, the activation of c-aminobutyric acid type A receptors, the inhibition of glutamate receptors, and the reduction of the extracellular glutamate concentrations by inhibiting Na channel-dependent glutamate release or the enhancement of glutamate uptake. In this study, our results demonstrated that propof
