Study on the expression of Cdc42、N-WASP、Arp2/3 in peripheral blood of patients with drug-resistant epilepsy_Journal of Epilepsy

Authors：

GUO Canshou ¹ , WANG Shuxin ¹ , ZANG Ruoshi ¹ , WEI Jin ¹ , ZHU Chunli ¹ ,  CHEN Xiaoqi ¹ ,  HUANG Jianmin ²

1. Department of Neurology,the Affiliated Hospital of Jianghan University, Wuhan 430015, China;
2. Department of Neurology,the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China;

Corresponding author：

CHEN Xiaoqi, Email: 838949111@qq.com; HUANG Jianmin, Email: bshuangjianmin@126.com

Keywords：

Drug resistance epilepsy; Cdc42; N-WASP; Arp2/3; Peripheral blood

DOI：

10.7507/2096-0247.20200002

Video：

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Object To investigate the pathogenesis of drug-resistant epilepsy by examining the expression of mRNA and protein of Cell Division Cycle 42 GTP-binding protein (Cdc42), Neural Wiskott-Aldrich Syndrome Protein (N-WASP) and Actin-related protein 2/3(Arp2/3) in peripheral blood of patients with drug-resistant epilepsy (DRE).Methods Seventy two essential epilepsy patients who were attended at outpatients and inpatients in the Department of Neurology of the Affiliated Hospital of Youjiang Medical University for Nationalities were selected from October 2016 to October 2018. According to the 2010 International League Against Epilepsy’s definition of Drug-Resistant Epilepsy, the patients were divided into 2 groups: 32 patients with DRE were defined as DRE group, 40 patients with anti-epilepsy drugs (AEDs) well controlled were defined as the well controlled group. Thirty two healthy persons were selected as control group. The expression of mRNA and protein of Cdc42, N-WASP and Arp2/3 in peripheral blood were measured by quantitative real-time PCR (RT-qPCR) and Western blot(WB). Experimental data were analyzed by ANOVA or rank-sum test.Results Compared with well-controlled group and healthy persons group, Cdc42, N-WASP, Arp2/3 in DRE group were significantly increased, the differences were statistically significant (P<0.05). Compared with the control group, Cdc42, N-WASP, Arp2/3 in well-controlled group were significantly increased, with statistically significant differences (P<0.05).Conclusion The expression of Cdc42, N-WASP, Arp2/3 in peripheral blood of patients with DRE significantly increased, being closely related to the occurrence and development of DRE, and used as indicators in peripheral blood predicting the occurrence of DRE.

Citation： GUO Canshou, WANG Shuxin, ZANG Ruoshi, WEI Jin, ZHU Chunli, CHEN Xiaoqi, HUANG Jianmin. Study on the expression of Cdc42、N-WASP、Arp2/3 in peripheral blood of patients with drug-resistant epilepsy. Journal of Epilepsy, 2020, 6(1): 7-11. doi: 10.7507/2096-0247.20200002 Copy

1.	Drew L. Gene therapy targets epilepsy. Nature, 2018, 564(7735): S10-S11.
2.	Xiao F, Wang X, Li J, et al. Overexpression of N-WASP in the brain of human epilepsy. Brain Res., 2008, 1233: 168-175.
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4.	Fang M, Xi ZQ, Wu Y, et al. A new hypothesis of drug refractory epilepsy: neural network hypothesis. Med Hypotheses, 2011, 76(6): 871-876.
5.	陈立颖, 汪仪, 陈忠. 颞叶癫痫与海马成体神经再生. 浙江大学学报(医学版), 2017, 46(1): 22-29.
6.	Danzer S. Mossy fiber sprouting in the epileptic brain: Taking on the lernaean hydra. Epilepsy Curr, 2017, 17(1): 50-51.
7.	Anton I M, Gomez-Oro C, Rivas S, et al. Crosstalk between WIP and rho family GTPases. Small GTPases, 2018: 1-7.
8.	Luan Q, Zelter A, Maccoss M, et al. Identification of Wiskott-aldrich syndrome protein (WASP) binding sites on the branched actin filament nucleator Arp2/3 complex. Proc Natl Acad Sci USA, 2018, 115(7): E1409-E1418.
9.	Novak N, Bar V, Sabanay H, et al. N-WASP is required for membrane wrapping and myelination by schwann cells. J Cell Biol, 2011, 192(2): 243-250.
10.	沈秀莲, 逯宜超, 甲芝莲, 等. N-WASP 通过 polyPro 和 VCA 结构域调控大脑皮层神经元迁移. 遗传, 2018, 40(5): 1-12.
11.	Hebbrecht T, Van Audenhove I, Zwaenepoel O, et al. VCA nanobodies target N-WASp to reduce invadopodium formation and functioning. PLoS One, 2017, 12(9): e0185076.
12.	Kitamura Y, Tsuchiya D, Takata K, et al. Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in alzheimer's disease. Neurosci Lett, 2003, 346(3): 149-152.
13.	Rotty JD, Wu C, Bear JE. New insights into the regulation and cellular functions of the ARP2/3 complex. Nat Rev Mol Cell Biol, 2013, 14(1): 7-12.
14.	Alekhina O, Burstein E, Billadeau D. Cellular functions of WASP family proteins at a glance. J Cell Sci, 2017, 130(14): 2235-2241.
15.	肖飞, 何梅, 王学峰, 等. 耐药性颞叶癫痫患者脑组织中 Cdc42 的表达. 中华医学杂志, 2007, 87(29): 2030-2032.
16.	Koyama R, Ikegaya Y. Mossy fiber sprouting as a potential therapeutic target for epilepsy. Curr Neurovasc Res, 2004, 1(1): 3-10.
17.	You J, Lin-Chao S. Gas7 functions with N-WASP to regulate the neurite outgrowth of hippocampal neurons. J Biol Chem, 2010, 285(15): 11652-11666.
18.	Cheng C, Mervis R, Niu S, et al. Insulin-like growth factor 1 is essential for normal dendritic growth. J Neurosci Res, 2003, 73(1): 1-9.

1. Drew L. Gene therapy targets epilepsy. Nature, 2018, 564(7735): S10-S11.
2. Xiao F, Wang X, Li J, et al. Overexpression of N-WASP in the brain of human epilepsy. Brain Res., 2008, 1233: 168-175.
3. Tang F, Hartz A M S, Bauer B. Drug-Resistant Epilepsy: Multiple hypotheses, Few answers. Front Neurol, 2017, 8: 301.
4. Fang M, Xi ZQ, Wu Y, et al. A new hypothesis of drug refractory epilepsy: neural network hypothesis. Med Hypotheses, 2011, 76(6): 871-876.
5. 陈立颖, 汪仪, 陈忠. 颞叶癫痫与海马成体神经再生. 浙江大学学报(医学版), 2017, 46(1): 22-29.
6. Danzer S. Mossy fiber sprouting in the epileptic brain: Taking on the lernaean hydra. Epilepsy Curr, 2017, 17(1): 50-51.
7. Anton I M, Gomez-Oro C, Rivas S, et al. Crosstalk between WIP and rho family GTPases. Small GTPases, 2018: 1-7.
8. Luan Q, Zelter A, Maccoss M, et al. Identification of Wiskott-aldrich syndrome protein (WASP) binding sites on the branched actin filament nucleator Arp2/3 complex. Proc Natl Acad Sci USA, 2018, 115(7): E1409-E1418.
9. Novak N, Bar V, Sabanay H, et al. N-WASP is required for membrane wrapping and myelination by schwann cells. J Cell Biol, 2011, 192(2): 243-250.
10. 沈秀莲, 逯宜超, 甲芝莲, 等. N-WASP 通过 polyPro 和 VCA 结构域调控大脑皮层神经元迁移. 遗传, 2018, 40(5): 1-12.
11. Hebbrecht T, Van Audenhove I, Zwaenepoel O, et al. VCA nanobodies target N-WASp to reduce invadopodium formation and functioning. PLoS One, 2017, 12(9): e0185076.
12. Kitamura Y, Tsuchiya D, Takata K, et al. Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in alzheimer's disease. Neurosci Lett, 2003, 346(3): 149-152.
13. Rotty JD, Wu C, Bear JE. New insights into the regulation and cellular functions of the ARP2/3 complex. Nat Rev Mol Cell Biol, 2013, 14(1): 7-12.
14. Alekhina O, Burstein E, Billadeau D. Cellular functions of WASP family proteins at a glance. J Cell Sci, 2017, 130(14): 2235-2241.
15. 肖飞, 何梅, 王学峰, 等. 耐药性颞叶癫痫患者脑组织中 Cdc42 的表达. 中华医学杂志, 2007, 87(29): 2030-2032.
16. Koyama R, Ikegaya Y. Mossy fiber sprouting as a potential therapeutic target for epilepsy. Curr Neurovasc Res, 2004, 1(1): 3-10.
17. You J, Lin-Chao S. Gas7 functions with N-WASP to regulate the neurite outgrowth of hippocampal neurons. J Biol Chem, 2010, 285(15): 11652-11666.
18. Cheng C, Mervis R, Niu S, et al. Insulin-like growth factor 1 is essential for normal dendritic growth. J Neurosci Res, 2003, 73(1): 1-9.

Journal of Epilepsy

Study on the expression of Cdc42、N-WASP、Arp2/3 in peripheral blood of patients with drug-resistant epilepsy

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