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Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells.
Brain Res Bull. 2018 06; 140:291-298.BR

Abstract

BACKGROUND

Sevoflurane has been extensively employed for induction and maintenance of general anesthesia. The effect of sevoflurane-induced apoptosis in developmental neurotoxicity has been appreciated for some time now, but the underlying mechanism of developmental neurotoxicity has not been established. The aim of our study is to evaluate the role of autophagy in sevoflurane-induced neurotoxicity through observing changes in the levels of autophagy in hippocampal neurons after exposure to sevoflurane.

METHODS/MATERIALS

Primary cultured hippocampus neuronal cells were exposed to either 3.4% sevoflurane for 1 h (S1h group), 3 h (S3h group), 5 h (S5h group), or air (control group). We observed changes in autophagy proteins Beclin-1, LC3-II, p62, and Beclin-1mRNA, LC3mRNA and SQSTM1mRNA using Western Blot and QRT-PCR. We also determined the expression of LC3 using immunofluorescence staining, monitored the occurrence of autophagy using RFP-GFP-LC3 expression plasmid transient transfected hippocampal neuronal cells, detected the expression of LC3-II using siRNA Knockdown Beclin-1 and Atg5, and determined changes in cell apoptosis using Annexin V/PI staining and flow cytometry.

RESULTS

After primary cultured hippocampal neuronal cells were exposed to 3.4% sevoflurane for 5 h, the expression level of Beclin-1 and LC3-II increased and p62 decreased in Western blotting. The expression of Beclin-1mRNA, LC3mRNA increased and SQSTM1mRNA decreased in QRT-PCR. LC3 increased with cell immunofluorescence staining, LC3 expression plasmid increased after mRFP-GFP-LC3 expression plasmid transient transfection and LC3-II decreased after transfection with siRNA Beclin-1 and siRNA Atg5. The apoptosis rate of primary cultured hippocampal neuronal cells increased in Annexin V/PI staining and flow cytometry analysis.

CONCLUSION

This study demonstrates that sevoflurane may induce hippocampal neuron autophagy in primary cultured hippocampal neuronal cell and that Beclin-1 and Atg5 are involved in the process of sevoflurane-induced autophagy. Exposure of sevoflurane may not only induce autophagy of hippocampal neurons but also activate the apoptosis of hippocampal neurons. Autophagy may play an important role in sevoflurane-induced neurotoxicity in primary cultured hippocampal neuronal cells.

Authors+Show Affiliations

Department of Anesthesiology, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.Department of Anesthesiology, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.Department of Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA.Department of Anesthesiology, The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. Electronic address: zryanmin@zju.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29857124

Citation

Xu, Lili, et al. "Role of Autophagy in Sevoflurane-induced Neurotoxicity in Neonatal Rat Hippocampal Cells." Brain Research Bulletin, vol. 140, 2018, pp. 291-298.
Xu L, Shen J, Yu L, et al. Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. Brain Res Bull. 2018;140:291-298.
Xu, L., Shen, J., Yu, L., Sun, J., McQuillan, P. M., Hu, Z., & Yan, M. (2018). Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. Brain Research Bulletin, 140, 291-298. https://doi.org/10.1016/j.brainresbull.2018.05.020
Xu L, et al. Role of Autophagy in Sevoflurane-induced Neurotoxicity in Neonatal Rat Hippocampal Cells. Brain Res Bull. 2018;140:291-298. PubMed PMID: 29857124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. AU - Xu,Lili, AU - Shen,Jianjun, AU - Yu,Lina, AU - Sun,Jianliang, AU - McQuillan,Patrick M, AU - Hu,Zhiyong, AU - Yan,Min, Y1 - 2018/05/29/ PY - 2018/01/29/received PY - 2018/05/17/revised PY - 2018/05/25/accepted PY - 2018/6/2/pubmed PY - 2019/5/31/medline PY - 2018/6/2/entrez KW - Apoptosis KW - Autophagy KW - Neurotoxicity KW - Sevoflurane SP - 291 EP - 298 JF - Brain research bulletin JO - Brain Res. Bull. VL - 140 N2 - BACKGROUND: Sevoflurane has been extensively employed for induction and maintenance of general anesthesia. The effect of sevoflurane-induced apoptosis in developmental neurotoxicity has been appreciated for some time now, but the underlying mechanism of developmental neurotoxicity has not been established. The aim of our study is to evaluate the role of autophagy in sevoflurane-induced neurotoxicity through observing changes in the levels of autophagy in hippocampal neurons after exposure to sevoflurane. METHODS/MATERIALS: Primary cultured hippocampus neuronal cells were exposed to either 3.4% sevoflurane for 1 h (S1h group), 3 h (S3h group), 5 h (S5h group), or air (control group). We observed changes in autophagy proteins Beclin-1, LC3-II, p62, and Beclin-1mRNA, LC3mRNA and SQSTM1mRNA using Western Blot and QRT-PCR. We also determined the expression of LC3 using immunofluorescence staining, monitored the occurrence of autophagy using RFP-GFP-LC3 expression plasmid transient transfected hippocampal neuronal cells, detected the expression of LC3-II using siRNA Knockdown Beclin-1 and Atg5, and determined changes in cell apoptosis using Annexin V/PI staining and flow cytometry. RESULTS: After primary cultured hippocampal neuronal cells were exposed to 3.4% sevoflurane for 5 h, the expression level of Beclin-1 and LC3-II increased and p62 decreased in Western blotting. The expression of Beclin-1mRNA, LC3mRNA increased and SQSTM1mRNA decreased in QRT-PCR. LC3 increased with cell immunofluorescence staining, LC3 expression plasmid increased after mRFP-GFP-LC3 expression plasmid transient transfection and LC3-II decreased after transfection with siRNA Beclin-1 and siRNA Atg5. The apoptosis rate of primary cultured hippocampal neuronal cells increased in Annexin V/PI staining and flow cytometry analysis. CONCLUSION: This study demonstrates that sevoflurane may induce hippocampal neuron autophagy in primary cultured hippocampal neuronal cell and that Beclin-1 and Atg5 are involved in the process of sevoflurane-induced autophagy. Exposure of sevoflurane may not only induce autophagy of hippocampal neurons but also activate the apoptosis of hippocampal neurons. Autophagy may play an important role in sevoflurane-induced neurotoxicity in primary cultured hippocampal neuronal cells. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/29857124/Role_of_autophagy_in_sevoflurane_induced_neurotoxicity_in_neonatal_rat_hippocampal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(18)30068-6 DB - PRIME DP - Unbound Medicine ER -