[1]袁 文,范春娥,陈宇琛,等.TMEM16A的表达下调对骨骼肌细胞分化的影响[J].南京师范大学学报(自然科学版),2020,43(03):106-111.[doi:10.3969/j.issn.1001-4616.2020.03.017]
　Yuan Wen,Fan Chune,Chen Yuchen,et al.The Effect of Down-Regulation of TMEM16A Expressionon Skeletal Muscle Cell Differentiation[J].Journal of Nanjing Normal University(Natural Science Edition),2020,43(03):106-111.[doi:10.3969/j.issn.1001-4616.2020.03.017]
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TMEM16A的表达下调对骨骼肌细胞分化的影响()
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《南京师范大学学报》（自然科学版）[ISSN:1001-4616/CN:32-1239/N]

卷:
第43卷
期数:
2020年03期
页码:
106-111
栏目:
·生物学·
出版日期:
2020-09-30

文章信息/Info

Title:
The Effect of Down-Regulation of TMEM16A Expressionon Skeletal Muscle Cell Differentiation
文章编号:
1001-4616(2020)03-0106-06
作者:
袁 文; 范春娥; 陈宇琛; 许艳华; 张茜茜; 孙志远; 陈华群
南京师范大学生命科学学院,江苏省分子医学生物技术重点实验室,江苏 南京 210023
Author(s):
Yuan Wen; Fan Chun’e; Chen Yuchen; Xu Yanhua; Zhang Qianqian; Sun Zhiyuan; Chen Huaqun
School of Life Sciences,Nanjing Normal University,Jiangsu Key Laboratory for Molecular and Medical Biotechnology,Nanjing 210023,China
关键词:
TMEM16A; T16Ainh-A01; C2C12; 成肌细胞; 生肌素
Keywords:
TMEM16A; T16A inh-A01; C2C12; myoblast; myogenin
分类号:
Q291
DOI:
10.3969/j.issn.1001-4616.2020.03.017
文献标志码:
A
摘要:
TMEM16A(Transmembrane Protein 16A)是一种钙离子(Ca2+)激活的氯离子通道(Calcium-activated Chloride Channels,CaCCs),在机体内广泛表达,具有重要的生理功能. 迄今为止,TMEM16A 在骨骼肌发育中的作用及机制尚无报道. 本研究利用TMEM16A特异性抑制剂T16Ainh-A01首次探讨了其表达下调对骨骼肌细胞分化的影响. 研究发现,T16Ainh-A01处理显著抑制C2C12和原代成肌细胞的肌分化. 进一步研究发现,T16Ainh-A01明显抑制肌分化过程中生肌素Myogenin的表达. 研究结果提示,TMEM16A的钙激活氯通道活性可能参与了骨骼肌细胞的分化过程,具体的作用机制有待进一步研究.
Abstract:
TMEM16A(Transmembrane Protein 16A)is one of the calcium(Ca2+)activated chloride channels(CaCCs). It is widely expressed in a variety of tissues and has important physiological functions. So far,the role of TMEM16A in the development of skeletal muscle has not been determined. In this study,we reported for the first time the effects down-regulation of TMEM16A on myogenic differentiation of myoblasts by using of the specific inhibitor T16Ainh-A01. We found that TMEM16A was apparently expressed both in myoblast cell line C2C12 and murine primary myoblast. We then determined that T16Ainh-A01 apparently inhibited the myogenic differentiation of both C2C12 and primary myoblasts. Furthermore,we showed that the expression of myogenin was obviously reduced in T16Ainh-A01 treated cells. Our results suggest that the calcium activated chloride channel activity of TMEM16A is involved in the myogenic differentiation of myoblast,the mechanisms under is still need to be investigated.

参考文献/References:

[1] HARTZELL C,ARREOLA J. Calcium-activated chloride channels[J]. Annual review of physiology,2005,67(1):719-758.
[2]TWYFFELS L,STRICKAERT A,VIRREIRA M,et al. Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte[J]. American journal of physiology cell physiology,2014,307(12):1102-1112.
[3]ANTONELLA C,EMANUELA C,LORETTA F,et al. TMEM16A,a membrane protein associated with calcium-dependent chloride channel activity[J]. Science,2008,322(5901):590-594.
[4]SCHROEDER B C,CHENG T,JAN Y N,et al. Expression cloning of TMEM16A as a calcium-activated chloride channel subunit[J]. Cell,2008,134(6):1019-1029.
[5]YOUNG D Y,HAWON C,JAE Y K,et al. TMEM16A confers receptor-activated calcium-dependent chloride conductance[J]. Nature,2008,455(7217):1210-125.
[6]KUNZELMANN K,KONGSUPHOL P,ALDEHNI F,et al. Bestrophin and TMEM16—Ca activated Cl channels with different functions[J]. Cell calcium,2009,46(4):233-241.
[7]OH U,JUNG J. Cellular functions of TMEM16/anoctamin[J]. Pflügers archiv-European journal of physiology,2016,468(3):1-11.
[8]MAZZONE A,EISENMAN S T,STREGE P R,et al. Inhibition of cell proliferation by a selective inhibitor of the Ca2+-activated Cl-channel,Ano1[J]. Biochemical & biophysical research communications,2012,427(2):248-253.
[9]STANICH J E,GIBBONS S J,EISENMAN S T,et al. Ano1 as a regulator of proliferation[J]. American journal of physiology gastrointestinal & liver physiology,2011,301(6):G1044.
[10]UMAMAHESWAR D,SHIWARSKI D J,DONG X,et al. TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression[J]. Cancer research,2012,72(13):3270-3781.
[11]BORIS M,AISTE T,PAOLO T. TMEM16A/anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells[J]. Journal of physiology,2010,588(13):2305-2314.
[12]DAYAL A,NG S F J,GRABNER M. Ca2+-activated Cl-channel TMEM16A/ANO1 identified in zebrafish skeletal muscle is crucial for action potential acceleration[J]. Nature communications,2019,10(1):1-15.
[13]RANDO A T. Primary mouse myoblast purification,characterization,and transplantation for cell-mediated gene therapy[J]. Journal of cell biology,1994,125(6):1275-1287.
[14]熊雷,何衍佶,戴威,等. 小鼠原代成肌细胞分离、纯化及培养[J]. 现代医药卫生,2017,33(3):23-25.
[15]ARTAZA J N,BHASIN S,MALLIDIS C,et al. Endogenous expression and localization of myostatin and its relation to myosin heavy chain distribution in C2C12 skeletal muscle cells[J]. Journal of cellular physiology,2002,190(2):170-179.
[16]CHAL J,POURQUI O. Making muscle:skeletal myogenesis in vivo and in vitro[J]. Development,2017,144(12):2104.
[17]WAN N,PUAY W,VERKMAN A S. TMEM16A inhibitors reveal TMEM16A as a minor component of calcium-activated chloride channel conductance in airway and intestinal epithelial cells[J]. Journal of biological chemistry,2011,286(3):2365-2374.
[18]MONCAUT N,RIGBY P W,CARVAJAL J J. Dial M(RF)for myogenesis[J]. Febs journal,2013,280(17):3980-3890.
[19]NABESHIMA Y,HANAOKA K,HAYASAKA M,et al. Myogenin gene disruption results in perinatal lethality because of severe muscle defect[J]. Nature,1993,364(6437):532-535.
[20]WHITE M M,AYLWIN M. Niflumic and flufenamic acids are potent reversible blockers of Ca2+-activated Cl-channels in Xenopus oocytes[J]. Molecular pharmacology,1990,37(5):720-724.
[21]SAYO M,SATOMI N,KATSUHIKO M,et al. Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells[J]. Journal of pharmacology & experimental therapeutics,2014,351(3):510-518.
[22]OTTOLIA M,TORO L. Potentiation of large conductance KCa channels by niflumic,flufenamic,and mefenamic acids[J]. Biophysical journal,1994,67(6):2272-2279.
[23]OH S J,HWANG S J,JUNG J,et al. MONNA,a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1[J]. Molecular pharmacology,2013,84(5):726-735.
[24]BOEDTKJER D M B,KIM S,JENSEN A B,et al. New selective inhibitors of calcium-activated chloride channels-T16A(inh)-A01,CaCC(inh)-A01 and MONNA—what do they inhibit?[J]. British journal of pharmacology,2015,172(16):4158-4172.
[25]DAVIS A J,SHI J,PRITCHARD H A,et al. Potent vasorelaxant activity of the TMEM16A inhibitor T16A(inh)-A01[J]. British journal of pharmacol,2013,168(3):773-784.
[26]ADRIAN B,ANKE B,HEIKE B,et al. Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling[J]. Proceedings of the national academy of sciences of the United States of America,2013,110(11):E1026-E1034.
[27]SONG Y,GAO J,GUAN L,et al. Inhibition of ANO1/TMEM16A induces apoptosis in human prostate carcinoma cells by activating TNF-α signaling[J]. Cell death & disease,2018,9(6):703.
[28]WEN L,MIN L,BAOGANG L,et al. Inhibition of Ca2+-activated Cl- channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma[J]. Cancer letters,2012,326(1):41-51.

备注/Memo

备注/Memo:
收稿日期:2019-06-03.
基金项目:国家自然科学基金项目(31371356)、江苏省教育厅重大项目(13KJA180004).
通讯作者:陈华群,教授,研究方向:细胞生物学. E-mail:chenhuaqun@njnu.edu.cn
更新日期/Last Update: 2020-09-15