Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2.

Guolin Lu,Yuping Wang,Dongdong Rao,Min Zhou,Sujing Zhang,Longxin Zhang,Liangpu Xu Liangpu Xu

doi:10.1155/2020/1587214

Abstract

Background Sevoflurane is commonly used as a general anesthetic in neonates to aged patients. Preconditioning or postconditioning with sevoflurane protects neurons from excitotoxic injury. Conversely, sevoflurane exposure induces neurotoxicity during early or late life. However, little is known about the underlying mechanism of the dual effect of sevoflurane on neurons. Autophagy is believed to control neuronal homeostasis. We hypothesized that autophagy determined the dual effect of sevoflurane on neurons. Methods DTome was used to identify the direct protein target (DPT) of sevoflurane. The STRING database was employed to investigate the proteins associated with the DPTs. Protein-protein interaction was assessed using Cytoscape. WebGestalt was used to analyze gene set enrichment. The linkage between candidate genes and autophagy was identified using GeneCards. Results This study found that 23 essential DPTs of sevoflurane interacted with 77 proteins from the STRING database. GABARAPL1 and 2, both of which are DPT- and autophagy-associated proteins, were significantly expressed in the brain and enriched in GABAergic synapses. Conclusions Taken together, our findings showed that the network of sevoflurane-DPT-GABARAPL1 and 2 is related to the dual effect of sevoflurane on neurons.

Highlights

Sevoflurane is commonly used as a general anesthetic in neonates to aged patients
In the STRING database, the direct protein target (DPT) identified from DTome were searched using a single protein name
After mapping in the STRING database, 77 proteins were identified as DPT-associated genes related to sevoflurane (Figure 1)

Summary

Introduction

Sevoflurane is commonly used as a general anesthetic in neonates to aged patients. Preconditioning or postconditioning with sevoflurane protects neurons from excitotoxic injury. Little is known about the underlying mechanism of the dual effect of sevoflurane on neurons. We hypothesized that autophagy determined the dual effect of sevoflurane on neurons. This study found that 23 essential DPTs of sevoflurane interacted with 77 proteins from the STRING database. GABARAPL1 and 2, both of which are DPT- and autophagy-associated proteins, were significantly expressed in the brain and enriched in GABAergic synapses. Either preconditioning or postconditioning with sevoflurane has been shown to exert a neuroprotective effect on cerebral ischemia injury in adult rodents [4,5,6]. Sevoflurane has a dual effect on neurons in the brain in different states. The mechanism underlying the dual effect of sevoflurane on neurons remains unclear

Methods

Results

Discussion

Conclusion