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Original Research

Open Access

CD82 Aggravates Sevoflurane - Induced Neurotoxicity by Regulating TRPM7 in Developing Neurons

  • Qing Shu1
  • Xiaoyan Zhao1
  • Xin Geng1
  • Xiaoye Wang2

1Department of Pharmacy, Ninth Hospital of Xi’an, Xi'an City, Shaanxi Province, 710054, P. R. China

2Department of Teaching Research, Ninth Hospital of Xi’an, Xi'an City, Shaanxi Province, 710054, P. R. China

DOI: 10.22514/sv.2020.16.0066 Vol.16,Issue 2,October 2020 pp.142-147

Published: 28 October 2020

*Corresponding Author(s): Xiaoye Wang E-mail:


Background: Sevoflurane, a commonly used anesthetic in neonatal, could induce neurotoxicity in newborn animals. CD82 was found to be involved in age-related cognitive impairment. However, the role of CD82 in sevoflurane-induced neurotoxicity remains elusive. Methods: Hippocampal neurons were isolated from neonatal rats (postnatal day 1 or 2), and then exposed to 1.8 % sevoflurane for 6, 12, 24 or 48 hours. Neurons were pre-transfected with siRNA targeting CD82 (siCD82) or co-transfected with siTRPM7 (transient receptor potential melastatin 7) and pcDNA 3.1-CD82, and then exposed with sevoflurane (1.8%, 12 hours). Cell viability of the neurons was analyzed with MTT assay, and cell apoptosis was determined by flow cytometry. Protein expression was analyzed by western blot. Results: Sevoflurane exposure decreased cell viability of the developing hippocampal neurons in a time-dependent manner. Protein expressions of CD82 and TRPM7 were increased in neurons post sevoflurane exposure in a time-dependent manner. Pre-transfection of siCD82 attenuated sevoflurane-induced decrease in cell viability and increase in cell apoptosis in the neurons. Moreover, knockdown of CD82 reversed the promoting effects of sevoflurane on protein expression of cleaved TRPM7 and cleaved caspase-3. Over-expression of CD82 aggravated sevoflurane-induced decrease in cell viability and increase in cell apoptosis in neurons, while knockdown of TRPM7 counteracted with the effects of CD82 over-expression on sevoflurane-induced developing neurons. Conclusion: Sevoflurane exposure increased the expression of CD82 and TRPM7 in developing hippocampal neurons, decreased cell viability and promoted the cell apoptosis. Knockdown of CD82 partially ameliorated sevoflurane-induced neurotoxicity by down-regulation of cleaved TRPM7 in the developing neurons.


CD82, TRPM7, Sevoflurane, Neurotoxicity, Neurons

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Qing Shu,Xiaoyan Zhao,Xin Geng,Xiaoye Wang. CD82 Aggravates Sevoflurane - Induced Neurotoxicity by Regulating TRPM7 in Developing Neurons. Signa Vitae. 2020. 16(2);142-147.


[1] Fredriksson A, Ponten E, Gordh T, et al. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology. 2007;107:427-436.

[2] Chen B, Deng X, Wang B, et al. Persistent neuronal apoptosis and synaptic loss induced by multiple but not single exposure of propofol contribute to long-term cognitive dysfunction in neonatal rats. J Toxicol Sci. 2016;41:627-636.

[3] Sprung J, Flick RP, Katusic SK, et al. Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia. Mayo Clin Proc. 2012;87:120-129.

[4] Liu B, Gu Y, Xiao H, et al. Altered Metabolomic Profiles May Be Associated with Sevoflurane-Induced Neurotoxicity in Neonatal Rats. Neurochemical Research. 2015;40:788-799.

[5] Termini CM, Cotter ML, Marjon KD, et al. The membrane scaffold CD82 regulates cell adhesion by altering alpha4 integrin stability and molecular density. Mol Biol Cell. 2014;25:1560-1573.

[6] Wang Y, Chen H, Fu Y, et al. MiR-195 inhibits proliferation and growth and induces apoptosis of endometrial stromal cells by targeting FKN. Int J Clin Exp Pathol. 2013;6:2824-2834.

[7] Mela A, Goldman JE. CD82 blocks cMet activation and overcomes hepa-tocyte growth factor effects on oligodendrocyte precursor differentiation. J Neurosci. 2013;33:7952-7960.

[8] Rojas-Hernandez CM, Nemunaitis J, Marjon KD, et al. Chronic lymphocytic leukemia with clinical debut as neurological involvement: a rare phenomenon and the need for better predictive markers. BMC hematology. 2017;17:3-3.

[9] Zhao Y, Kiss T, DelFavero J, et al. CD82-TRPM7-Numb signaling mediates age-related cognitive impairment. Geroscience. 2020;42:595-611.

[10] Park HS, Hong C, Kim BJ, et al. The Pathophysiologic Roles of TRPM7 Channel. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology. 2014;18:15-23.

[11] Abumaria N, Li W, Clarkson AN. Role of the chanzyme TRPM7 in the nervous system in health and disease. Cell Mol Life Sci. 2019;76:3301-3310.

[12] Kim Y, Oh HG, Cho YY, et al. Stress hormone potentiates Zn(2+)-induced neurotoxicity via TRPM7 channel in dopaminergic neuron. Biochem Biophys Res Commun. 2016;470:362-367.

[13] Chen W, Xu B, Xiao A, et al. TRPM7 inhibitor carvacrol protects brain from neonatal hypoxic-ischemic injury. Mol Brain. 2015;8:11.

[14] Wu J, Yang JJ, Cao Y, et al. Iron overload contributes to general anaesthesia-induced neurotoxicity and cognitive deficits. J Neuroinflam-mation. 2020;17:110.

[15] Sun HS, Jackson MF, Martin LJ, et al. Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci. 2009;12:1300-1307.

[16] Zhou X, Lu D, Li WD, et al. Sevoflurane Affects Oxidative Stress and Alters Apoptosis Status in Children and Cultured Neural Stem Cells. Neurotox Res. 2018;33:790-800.

[17] Qi J, Jia Y, Wang W, et al. The role of Bag2 in neurotoxicity induced by the anesthetic sevoflurane. J Cell Biochem. 2018.

[18] Abiria SA, Krapivinsky G, Sah R, et al. TRPM7 senses oxidative stress to release Zn(2+) from unique intracellular vesicles. Proceedings of the National Academy of Sciences of the United States of America. 2017;114:E6079-E6088.

[19] 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.

[20] Khan NS, Lukason DP, Feliu M, et al. CD82 controls CpG-dependent TLR9 signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33:12500-12514.

[21] Oh HG, Chun YS, Park CS, et al. Regulation of basal autophagy by transient receptor potential melastatin 7 (TRPM7) channel. Biochem Biophys Res Commun. 2015;463:7-12.

[22] Desai BN, Krapivinsky G, Navarro B, et al. Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis. Developmental cell. 2012;22:1149-1162.

[23] Kim BJ, Park EJ, Lee JH, et al. Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer. Cancer Sci. 2008;99:2502-2509.

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