Abnormal changes in voltage-gated sodium channels subtypes NaV1.1, NaV1.2, NaV1.3, NaV1.6 and CaM/CaMKII pathway in low-grade astrocytoma

被引：6

作者：

Guan, Gefei ^{[1
,2
]}

Zhao, Mingyi ^{[3
]}

Xu, Xiaoxue ^{[4
]}

Boczek, Tomasz ^{[5
]}

Mao, Xiaoyuan ^{[6
,7
]}

Li, Zhi ^{[1
]}

Gao, Qinghua ^{[1
]}

Li, Jianing ^{[1
]}

Zhao, Dongyi ^{[1
]}

Niu, Wanting ^{[8
]}

Lei, Liming ^{[9
]}

Guo, Feng ^{[1
]}

机构：

[1] China Med Univ, Sch Pharm, Dept Pharmaceut Toxicol, Shenyang 110122, Liaoning, Peoples R China

[2] China Med Univ, Hosp 1, Dept Neurosurg, Shenyang 110001, Liaoning, Peoples R China

[3] Cent S Univ, Xiangya Hosp 3, Dept Pediat, Changsha 410006, Hunan, Peoples R China

[4] China Med Univ, Hosp 1, Dept Neurol, Shenyang 110001, Liaoning, Peoples R China

[5] Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA

[6] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China

[7] Cent S Univ, Hunan Key Lab Pharmacogenet, Inst Clin Pharmacol, Changsha 410078, Hunan, Peoples R China

[8] Harvard Med Sch, Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA

[9] Guangdong Acad Med Sci, Surg Guangdong Cardiovasc Inst, Guangdong Gen Hosp, Lab South China Struct Heart Dis,Dept Cardiovasc, Guangzhou 510080, Guangdong, Peoples R China

来源：

NEUROSCIENCE LETTERS | 2018年 / 674卷

关键词：

Seizure; Low-grade astrocytoma; VGSCs; CaM; CaMKII; PROTEIN-KINASE-II; ION CHANNELS; DRAVET SYNDROME; NA+ CHANNELS; EXPRESSION; EPILEPSY; INHIBITION; NEURONS; MODEL; RAT;

D O I：

10.1016/j.neulet.2018.03.047

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Epileptic seizures are the main clinical manifestation of low-grade astrocytoma. Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. Until now, the role of VGSCs and the relationships between calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII) and VGSCs in low-grade astrocytoma have not been demonstrated. In our study, the protein expression of Na(V)1.3, Na(V)1.6 and CaM was significantly increased in the tumor compared to control tissue, while the level of p-CaMKII/CaMKII was significantly decreased in the tumor group as determined by Western Blotting and immunohistochemistry. Furthermore, double-labeling immuno-fluorescence results showed that Na(V)1.3/Na(V)1.6 and CaM co-localization was significantly increased in the tumor group compared to control tissue. This study represents the first evidence of the abnormal changes in VGSCs subtypes and CaM/CaMKII pathway in human brain low-grade astrocytoma, providing new potential targets for molecular therapies of this disease.

引用

页码：148 / 155

页数：8

共 34 条

[1] Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Inhibition Induces Neurotoxicity via Dysregulation of Glutamate/Calcium Signaling and Hyperexcitability [J].

Ashpole, Nicole M. ;

Song, Weihua ;

Brustovetsky, Tatiana ;

Engleman, Eric A. ;

Brustovetsky, Nickolay ;

Cummins, Theodore R. ;

Hudmon, Andy .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (11) :8495-8506

[2] THE PERINODAL ASTROCYTE [J].

BLACK, JA ;

WAXMAN, SG .

GLIA, 1988, 1 (03) :169-183

[3] Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5 [J].

Black, Joel A. ;

Newcombe, Jia ;

Waxman, Stephen G. .

BRAIN, 2010, 133 :835-846

[4] International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels [J].

Catterall, WA ;

Goldin, AL ;

Waxman, SG .

PHARMACOLOGICAL REVIEWS, 2005, 57 (04) :397-409

[5] Correlations in timing of sodium channel expression, epilepsy, and sudden death in Dravet syndrome [J].

Cheah, Christine S. ;

Westenbroek, Ruth E. ;

Roden, William H. ;

Kalume, Franck ;

Oakley, John C. ;

Jansen, Laura A. ;

Catterall, William A. .

CHANNELS, 2013, 7 (06) :468-472

[6] Prolonged changes in Ca 2+/calmodulin-dependent protein kinase II after a brief pentylenetetrazol seizure;: potential role in kindling [J].

Dong, Y ;

Rosenberg, HC .

EPILEPSY RESEARCH, 2004, 58 (2-3) :107-117

[7] Early-life febrile seizures worsen adult phenotypes in Scn1a mutants [J].

Dutton, Stacey B. B. ;

Dutt, Karoni ;

Papale, Ligia A. ;

Helmers, Sandra ;

Goldin, Alan L. ;

Escayg, Andrew .

EXPERIMENTAL NEUROLOGY, 2017, 293 :159-171

[8] Voltage-gated sodium channel Nav 1.1, Nav 1.3 and β1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat [J].

Guo, Feng ;

Yu, Na ;

Cai, Ji-Qun ;

Quinn, Tim ;

Zong, Zhi-Hong ;

Zeng, Yan-Jun ;

Hao, Li-Ying .

BRAIN RESEARCH BULLETIN, 2008, 75 (01) :179-187

[9] Low-Mg2+ treatment increases sensitivity of voltage-gated Na+ channels to Ca2+/calmodulin-mediated modulation in cultured hippocampal neurons [J].

Guo, Feng ;

Zhou, Pei-Dong ;

Gao, Qing-Hua ;

Gong, Jian ;

Feng, Rui ;

Xu, Xiao-Xue ;

Liu, Shu-Yuan ;

Hu, Hui-Yuan ;

Zhao, Mei-Mi ;

Adam, Hogan-Cann ;

Cai, Ji-Qun ;

Hao, Li-Ying .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2015, 308 (08) :C594-C605

[10] The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model [J].

Guo, Feng ;

Xu, Xiaoxue ;

Cai, Jiqun ;

Hu, Huiyuan ;

Sun, Wei ;

He, Guilin ;

Shao, Dongxue ;

Wang, Lei ;

Chen, Tianbao ;

Shaw, Chris ;

Zhu, Tong ;

Hao, Liying .

NEUROCHEMISTRY INTERNATIONAL, 2013, 62 (03) :287-295

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