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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Neuroprotective Effect of Dexmedetomidine Pretreatment on Sevoflurane- Initiated Neurotoxicity Via the Mir-204-5p/SOX4 Axis

Author(s): Run Wang, Pengfei Liu, Fan Li and Hui Qiao*

Volume 30, Issue 7, 2023

Published on: 03 July, 2023

Page: [608 - 618] Pages: 11

DOI: 10.2174/0929866530666230530164913

Price: $65

Abstract

Background: Sevoflurane (Sev) is a type of volatile anesthetic commonly used in clinic practices and can initiate long-term neurotoxicity, while dexmedetomidine (Dex) possesses a neuroprotective function in multiple neurological disorders.

Objective: This work expounded on the function of Dex pretreatment in Sev-initiated neurotoxicity.

Methods: At first, human neuroblastoma cells (SK-N-SH cells) were treated with different concentrations of Sev or Dex, followed by the cell counting kit (CCK)-8 assay to decide the appropriate concentrations of Sev or Dex. Cell viability, lactate dehydrogenase (LDH) productions, and apoptotic rate of SK-N-SH cells were examined by the CCK-8 assay, LDH cytotoxicity kit, and flow cytometry assay in sequence. Further, reactive oxygen species (ROS) levels and proinflammatory cytokine contents were examined by the ROS assay kit and the enzyme-linked immunosorbent assay kits. The expression patterns of microRNA (miR)-204-5p and SRY-box transcription factor 4 (SOX4) in SK-N-SH cells were measured by real-time quantitative polymerase chain reaction or Western blotting. The binding relationship between miR-204-5p and SOX4 was confirmed by the dual-luciferase assay. After transfection of miR-204-5p mimics or SOX4 siRNA, the role of the miR-204-5p/SOX4 axis in Sev-initiated neurotoxicity was detected.

Results: Sev treatment reduced SK-N-SH cell viability in a concentration-dependent manner, and Dex pretreatment diminished Sev-initiated neurotoxicity. Mechanically, Dex pretreatment limited Sevinduced upregulation of miR-204-5p and further increased SOX4 expression levels. miR-204-5p upregulation or SOX4 knockdown averted the neuroprotection function of Dex pretreatment in Sevinitiated neurotoxicity.

Conclusion: Dex pretreatment decreased miR-204-5p expression levels and upregulated SOX4 expression levels, palliating Sev-initiated neurotoxicity.

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[1]
Costi, D.; Cyna, A.M.; Ahmed, S.; Stephens, K.; Strickland, P.; Ellwood, J.; Larsson, J.N.; Chooi, C.; Burgoyne, L.L.; Middleton, P. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Libr., 2014, (9), CD007084.
[http://dx.doi.org/10.1002/14651858.CD007084.pub2] [PMID: 25212274]
[2]
Wang, H.Y.; Chen, T.Y.; Li, D.J.; Lin, P.Y.; Su, K.P.; Chiang, M.H.; Carvalho, A.F.; Stubbs, B.; Tu, Y.K.; Wu, Y.C.; Roerecke, M.; Smith, L.; Tseng, P.T.; Hung, K.C. Association of pharmacological prophylaxis with the risk of pediatric emergence delirium after sevoflurane anesthesia: An updated network meta-analysis. J. Clin. Anesth., 2021, 75, 110488.
[http://dx.doi.org/10.1016/j.jclinane.2021.110488] [PMID: 34481361]
[3]
Wang, C.; Chen, W.; Zhang, Y.; Lin, S.; He, H. Update on the mechanism and treatment of sevoflurane-induced postoperative cognitive dysfunction. Front. Aging Neurosci., 2021, 13, 702231.
[http://dx.doi.org/10.3389/fnagi.2021.702231] [PMID: 34305576]
[4]
Apai, C.; Shah, R.; Tran, K.; Shah, P.S. Anesthesia and the developing brain: A review of sevoflurane-induced neurotoxicity in pediatric populations. Clin. Ther., 2021, 43(4), 762-778.
[http://dx.doi.org/10.1016/j.clinthera.2021.01.024] [PMID: 33674065]
[5]
Sun, M.; Xie, Z.; Zhang, J.; Leng, Y. Mechanistic insight into sevoflurane-associated developmental neurotoxicity. Cell Biol. Toxicol., 2022, 38, 927-943.
[http://dx.doi.org/10.1007/s10565-021-09677-y] [PMID: 34766256]
[6]
Mondardini, M.C.; Amigoni, A.; Cortellazzi, P.; Di Palma, A.; Navarra, C.; Picardo, S.G.; Puzzutiello, R.; Rinaldi, L.; Vitale, F.; Zito Marinosci, G.; Conti, G. Intranasal dexmedetomidine in pediatrics: Update of current knowledge. Minerva Anestesiol., 2019, 85(12), 1334-1345.
[http://dx.doi.org/10.23736/S0375-9393.19.13820-5] [PMID: 31630510]
[7]
Hoffman, J.; Hamner, C. Effectiveness of dexmedetomidine use in general anesthesia to prevent postoperative shivering: A systematic review. JBI Database Syst. Rev. Implement. Reports, 2015, 13(12), 287-313.
[http://dx.doi.org/10.11124/jbisrir-2015-2257] [PMID: 26767820]
[8]
Wu, X.; Hang, L.H.; Wang, H.; Shao, D.H.; Xu, Y.G.; Cui, W.; Chen, Z. Intranasally administered adjunctive dexmedetomidine reduces perioperative anesthetic requirements in general anesthesia. Yonsei Med. J., 2016, 57(4), 998-1005.
[http://dx.doi.org/10.3349/ymj.2016.57.4.998] [PMID: 27189297]
[9]
Unchiti, K.; Leurcharusmee, P.; Samerchua, A.; Pipanmekaporn, T.; Chattipakorn, N.; Chattipakorn, S.C. The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies. Eur. J. Neurosci., 2021, 54(9), 7006-7047.
[http://dx.doi.org/10.1111/ejn.15474] [PMID: 34561931]
[10]
Yang, F.; Zhao, H.; Zhang, K.; Wu, X.; Liu, H. Research progress and treatment strategies for anesthetic neurotoxicity. Brain Res. Bull., 2020, 164, 37-44.
[http://dx.doi.org/10.1016/j.brainresbull.2020.08.003] [PMID: 32798600]
[11]
Suo, L.; Wang, M. Dexmedetomidine alleviates sevoflurane-induced neurotoxicity via mitophagy signaling. Mol. Biol. Rep., 2020, 47(10), 7893-7901.
[http://dx.doi.org/10.1007/s11033-020-05868-8] [PMID: 33044702]
[12]
Saliminejad, K.; Khorshid, K.H.R.; Fard, S.S.; Ghaffari, S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol., 2019, 234(5), 5451-5465.
[http://dx.doi.org/10.1002/jcp.27486] [PMID: 30471116]
[13]
Jauhari, A.; Singh, T.; Yadav, S. Neurodevelopmental disorders and neurotoxicity: MicroRNA in focus. J. Chem. Neuroanat., 2022, 120, 102072.
[http://dx.doi.org/10.1016/j.jchemneu.2022.102072] [PMID: 35063638]
[14]
Zhou, S.; Zhang, D.; Guo, J.; Chen, Z.; Chen, Y.; Zhang, J. Long non‐coding RNA NORAD functions as a MICRORNA‐204‐5P sponge to repress the progression of Parkinson’s disease in vitro by increasing the solute carrier family 5 member 3 expression. IUBMB Life, 2020, 72(9), 2045-2055.
[http://dx.doi.org/10.1002/iub.2344] [PMID: 32687247]
[15]
Liu, H.; Wang, J.; Yan, R.; Jin, S.; Wan, Z.; Cheng, J.; Li, N.; Chen, L.; Le, C. MicroRNA-204-5p mediates sevoflurane-induced cytotoxicity in HT22 cells by targeting brain-derived neurotrophic factor. Histol. Histopathol., 2020, 35(11), 1353-1361.
[http://dx.doi.org/10.14670/HH-18-266] [PMID: 33006132]
[16]
Xu, S.; Gao, R.; Chen, L. Dexmedetomidine regulates sevoflurane‐induced neurotoxicity through the miR‐330‐3p/ULK1 axis. J. Biochem. Mol. Toxicol., 2021, 35(12), e22919.
[http://dx.doi.org/10.1002/jbt.22919] [PMID: 34590382]
[17]
Moreno, C.S. SOX4: The unappreciated oncogene. Semin. Cancer Biol., 2020, 67(Pt 1), 57-64.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.027] [PMID: 31445218]
[18]
Kavyanifar, A.; Turan, S.; Lie, D.C. SoxC transcription factors: Multifunctional regulators of neurodevelopment. Cell Tissue Res., 2018, 371(1), 91-103.
[http://dx.doi.org/10.1007/s00441-017-2708-7] [PMID: 29079881]
[19]
Zhao, Y.; Ai, Y. Overexpression of lncRNA Gm15621 alleviates apoptosis and inflammation response resulting from sevoflurane treatment through inhibiting miR‐133a/Sox4. J. Cell. Physiol., 2020, 235(2), 957-965.
[http://dx.doi.org/10.1002/jcp.29011] [PMID: 31264218]
[20]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(D1), D92-D97.
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[21]
Huang, H.Y.; Lin, Y.C.D.; Li, J.; Huang, K.Y.; Shrestha, S.; Hong, H.C.; Tang, Y.; Chen, Y.G.; Jin, C.N.; Yu, Y.; Xu, J.T.; Li, Y.M.; Cai, X.X.; Zhou, Z.Y.; Chen, X.H.; Pei, Y.Y.; Hu, L.; Su, J.J.; Cui, S.D.; Wang, F.; Xie, Y.Y.; Ding, S.Y.; Luo, M.F.; Chou, C.H.; Chang, N.W.; Chen, K.W.; Cheng, Y.H.; Wan, X.H.; Hsu, W.L.; Lee, T.Y.; Wei, F.X.; Huang, H.D. miRTarBase 2020: Updates to the experimentally validated microRNA–target interaction database. Nucleic Acids Res., 2019, 48(D1), gkz896.
[http://dx.doi.org/10.1093/nar/gkz896] [PMID: 31647101]
[22]
Miranda, K.C.; Huynh, T.; Tay, Y.; Ang, Y.S.; Tam, W.L.; Thomson, A.M.; Lim, B.; Rigoutsos, I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell, 2006, 126(6), 1203-1217.
[http://dx.doi.org/10.1016/j.cell.2006.07.031] [PMID: 16990141]
[23]
Chen, Y.; Wang, X. miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res., 2020, 48(D1), D127-D131.
[http://dx.doi.org/10.1093/nar/gkz757] [PMID: 31504780]
[24]
Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015, 4, e05005.
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[25]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[26]
Liu, X.; Ji, J.; Zhao, G.Q. General anesthesia affecting on developing brain: Evidence from animal to clinical research. J. Anesth., 2020, 34(5), 765-772.
[http://dx.doi.org/10.1007/s00540-020-02812-9] [PMID: 32601887]
[27]
Huang, X.; Ying, J.; Yang, D.; Fang, P.; Wang, X.; Zhou, B.; Zhang, L.; Fang, Y.; Yu, W.; Liu, X.; Zhen, Q.; Hua, F. The mechanisms of sevoflurane-induced neuroinflammation. Front. Aging Neurosci., 2021, 13, 717745.
[http://dx.doi.org/10.3389/fnagi.2021.717745] [PMID: 34421578]
[28]
Neag, M.A.; Mitre, A.O.; Catinean, A.; Mitre, C.I. An overview on the mechanisms of neuroprotection and neurotoxicity of isoflurane and sevoflurane in experimental studies. Brain Res. Bull., 2020, 165, 281-289.
[http://dx.doi.org/10.1016/j.brainresbull.2020.10.011] [PMID: 33080307]
[29]
Liaquat, Z.; Xu, X.; Zilundu, P.L.M.; Fu, R.; Zhou, L. The current role of dexmedetomidine as neuroprotective Agent: An updated review. Brain Sci., 2021, 11(7), 846.
[http://dx.doi.org/10.3390/brainsci11070846] [PMID: 34202110]
[30]
Colak, R.; Celik, A.; Diniz, G.; Alkan Ozdemir, S.; Yilmaz, O.; Calkavur, S. Evaluation of the neuroprotective effect of pycnogenol in a hypoxic-ischemic brain injury model in newborn rats. Am. J. Perinatol., 2023, 40(06), 612-618.
[http://dx.doi.org/10.1055/s-0041-1730349] [PMID: 34044458]
[31]
Ding, X.; Cao, Y.; Li, L.; Zhao, G. Dexmedetomidine reduces the lidocaine-induced neurotoxicity by inhibiting inflammasome activation and reducing pyroptosis in rats. Biol. Pharm. Bull., 2021, 44(7), 902-909.
[http://dx.doi.org/10.1248/bpb.b20-00482] [PMID: 34193687]
[32]
Sun, W.; Wang, J.; Cai, D.; Pei, L. Neuroprotection of the developing brain by dexmedetomidine is mediated by attenuating single propofol-induced hippocampal apoptosis and synaptic plasticity deficits. Exp. Neurobiol., 2020, 29(5), 356-375.
[http://dx.doi.org/10.5607/en20032] [PMID: 33154198]
[33]
Bo, L.J.; Yu, P.X.; Zhang, F.Z.; Dong, Z.M. Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus. J. Anesth., 2018, 32(5), 717-724.
[http://dx.doi.org/10.1007/s00540-018-2545-1] [PMID: 30128750]
[34]
Wang, N.; Wang, M. Dexmedetomidine suppresses sevoflurane anesthesia-induced neuroinflammation through activation of the PI3K/Akt/mTOR pathway. BMC Anesthesiol., 2019, 19(1), 134.
[http://dx.doi.org/10.1186/s12871-019-0808-5] [PMID: 31351473]
[35]
Shan, Y.; Sun, S.; Yang, F.; Shang, N.; Liu, H. Dexmedetomidine protects the developing rat brain against the neurotoxicity wrought by sevoflurane: Role of autophagy and Drp1–Bax signaling. Drug Des. Devel. Ther., 2018, 12, 3617-3624.
[http://dx.doi.org/10.2147/DDDT.S180343] [PMID: 30464393]
[36]
Tal, T.L.; Tanguay, R.L. Non-coding RNAs—Novel targets in neurotoxicity. Neurotoxicology, 2012, 33(3), 530-544.
[http://dx.doi.org/10.1016/j.neuro.2012.02.013] [PMID: 22394481]
[37]
Su, R.; Sun, P.; Zhang, D.; Xiao, W.; Feng, C.; Zhong, L. Neuroprotective effect of miR-410-3p against sevoflurane anesthesia-induced cognitive dysfunction in rats through PI3K/Akt signaling pathway via targeting C–X–C motif chemokine receptor 5. Genes Genomics, 2019, 41(10), 1223-1231.
[http://dx.doi.org/10.1007/s13258-019-00851-5] [PMID: 31350734]
[38]
Chen, Y.; Gao, X.; Pei, H. miRNA‐384‐3p alleviates sevoflurane‐induced nerve injury by inhibiting Aak1 kinase in neonatal rats. Brain Behav., 2022, 12(7), e2556.
[http://dx.doi.org/10.1002/brb3.2556] [PMID: 35726359]
[39]
Wang, Q.; She, Y.; Bi, X.; Zhao, B.; Ruan, X.; Tan, Y. Dexmedetomidine protects pc12 cells from lidocaine-induced cytotoxicity through downregulation of COL3A1 mediated by mirlet-7b. DNA Cell Biol., 2017, 36(7), 518-528.
[http://dx.doi.org/10.1089/dna.2016.3623] [PMID: 28436683]
[40]
Chen, Z.; Ding, Y.; Zeng, Y.; Zhang, X.P.; Chen, J.Y. Dexmedetomidine reduces propofol-induced hippocampal neuron injury by modulating the miR-377-5p/Arc pathway. BMC Pharmacol. Toxicol., 2022, 23(1), 18.
[http://dx.doi.org/10.1186/s40360-022-00555-9] [PMID: 35337381]
[41]
Xue, Y.; Xu, T.; Jiang, W. Dexmedetomidine protects PC12 cells from ropivacaine injury through miR-381/LRRC4/SDF-1/CXCR4 signaling pathway. Regen. Ther., 2020, 14, 322-329.
[http://dx.doi.org/10.1016/j.reth.2020.03.001] [PMID: 32467829]
[42]
Chiu, C.C.; Yeh, T.H.; Chen, R.S.; Chen, H.C.; Huang, Y.Z.; Weng, Y.H.; Cheng, Y.C.; Liu, Y.C.; Cheng, A.J.; Lu, Y.C.; Chen, Y.J.; Lin, Y.W.; Hsu, C.C.; Chen, Y.L.; Lu, C.S.; Wang, H.L. Upregulated expression of microRNA-204-5p leads to the death of dopaminergic cells by targeting dyrk1a-mediated apoptotic signaling cascade. Front. Cell. Neurosci., 2019, 13, 399.
[http://dx.doi.org/10.3389/fncel.2019.00399] [PMID: 31572127]
[43]
Liu, H.; Wang, M.; Xu, L.; Li, M.; Zhao, M. Neuroprotective effect of miR-204-5p downregulation against isoflurane-induced learning and memory impairment via targeting EphB2 and inhibiting neuroinflammation. Hum. Exp. Toxicol., 2021, 40(10), 1746-1754.
[http://dx.doi.org/10.1177/09603271211009970] [PMID: 33878909]
[44]
Stevanovic, M.; Drakulic, D.; Lazic, A.; Ninkovic, D.S.; Schwirtlich, M.; Mojsin, M. SOX transcription factors as important regulators of neuronal and glial differentiation during nervous system development and adult neurogenesis. Front. Mol. Neurosci., 2021, 14, 654031.
[http://dx.doi.org/10.3389/fnmol.2021.654031] [PMID: 33867936]
[45]
Mu, L.; Berti, L.; Masserdotti, G.; Covic, M.; Michaelidis, T.M.; Doberauer, K.; Merz, K.; Rehfeld, F.; Haslinger, A.; Wegner, M.; Sock, E.; Lefebvre, V.; Couillard-Despres, S.; Aigner, L.; Berninger, B.; Lie, D.C. SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis. J. Neurosci., 2012, 32(9), 3067-3080.
[http://dx.doi.org/10.1523/JNEUROSCI.4679-11.2012] [PMID: 22378879]
[46]
Wang, Y.; Xie, J.; Liu, W.; Zhang, R.; Huang, S.; Xing, Y. Lidocaine sensitizes the cytotoxicity of 5-fluorouacil in melanoma cells via upregulation of microRNA-493. Pharmazie, 2017, 72(11), 663-669.
[http://dx.doi.org/10.1691/ph.2017.7616] [PMID: 29442040]
[47]
Du, Q.; Liu, J.; Zhang, X.; Zhang, X.; Zhu, H.; Wei, M.; Wang, S. Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells. Braz. J. Med. Biol. Res., 2018, 51(4), e6803.
[http://dx.doi.org/10.1590/1414-431x20176803] [PMID: 29490000]
[48]
Xu, E.; Hu, M.; Ge, R.; Tong, D.; Fan, Y.; Ren, X.; Liu, Y. LncRNA-42060 regulates tamoxifen sensitivity and tumor development via regulating the mir-204-5p/sox4 axis in canine mammary gland tumor cells. Front. Vet. Sci., 2021, 8, 654694.
[http://dx.doi.org/10.3389/fvets.2021.654694] [PMID: 34235197]
[49]
Li, P.; Zhong, X.; Zhang, L.; Yu, Y.; Niu, J. Bioinformatic investigation for candidate genes and molecular mechanism in the pathogenesis of membranous nephropathy. Nephrology, 2021, 26(3), 262-269.
[http://dx.doi.org/10.1111/nep.13833] [PMID: 33207024]

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