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Metab Brain Dis. 2015 Oct;30(5):1161-6. doi: 10.1007/s11011-015-9673-1. Epub 2015 May 15.

Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity.

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Department of Anesthesia, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan, 250012, China,


Sevoflurane, one of the most commonly used volatile anesthetics in clinical treatment, has been shown to induce a widespread increase in brain apoptosis. However, the underlying mechanism is still unknown. Sestrin 2 has been recently shown to regulate intracellular reactive oxygen species (ROS) levels and play a crucial role in p53-dependent antioxidant defenses. In this study, our results indicated that administration of Sevoflurane elevated the gene and protein expression of Sestrin-2 in a dose dependent manner in human neuroblastoma M17 cells. It was shown that silence of Sestrin-2 by small RNA interference (siRNA) ominously exacerbated the increase in intracellular ROS and reduction of SOD activity induced by Sevoflurane treatment. Notably, knockdown of Sestrin-2 in M17 cells significantly increases the number of apoptotic cells after treatment with Sevoflurane. Mechanistically, we also found that Sevoflurane treatment resulted in a reduced amount of the cytosolic anti-apoptotic protein Bcl-2 but an increased amount of Bax, which was exacerbated by knockdown of Sestrin-2. In addition, knockdown of Sestrin-2 remarkably increased the elevated cleaved Caspase-3 expression. Finally, we showed that the induction of Sestrin-2 by Sevoflurane was mediated by p53. These results suggest that the suppressive effects of Sestrin-2 on neuroapoptosis against the Sevoflurane anesthesia in neuronal cells might be associated with modulation of mitochondrial pathway.

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