Article Data

  • Views 173
  • Dowloads 14

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:

PDF (662.2 kB)


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.

Key words

CD82, TRPM7, Sevoflurane, Neurotoxicity, Neurons

Cite And Share

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.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) The Science Citation Index (SCI) is a citation index originally produced by the Institute for Scientific Information (ISI) and created by Eugene Garfield. It (Science Citation Index Expanded) covers more than 8,500 notable and significant journals, across 150 disciplines in science and technology, from 1900 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time