title: The ClC-3 chloride channel associated with microtubules is a target of paclitaxel in its induced-apoptosis.
abstract: Recent evidences show that cationic fluxes play a pivotal role in cell apoptosis. In this study, the roles of Cl(-) channels in paclitaxel-induced apoptosis were investigated in nasopharyngeal carcinoma CNE-2Z cells. Chloride current and apoptosis were induced by paclitaxel and inhibited by chloride channel blockers. Paclitaxel-activated current possessed similar properties to volume-activated chloride current. After ClC-3 was knocked-down by ClC-3-siRNA, hypotonicity-activated and paclitaxel-induced chloride currents were obviously decreased, indicating that the chloride channel involved in paclitaxel-induced apoptosis may be ClC-3. In early apoptotic cells, ClC-3 was up-regulated significantly; over-expressed ClC-3 was accumulated in cell membrane to form intercrossed filaments, which were co-localized with α-tubulins; changes of ultrastructures and decrease of flexibility in cell membrane were detected by atomic force microscopy. These suggest that ClC-3 is a critical target of paclitaxel and the involvement of ClC-3 in apoptosis may be associated with its accumulation with membrane microtubules and its over activation.
authors.affiliation: 1] Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China [2] Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China [3].
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Huarong
authors.initials: H
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Deng
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Bai
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport; D034622:RNA Interference; D014404:Tubulin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D065101:Chloride Channel Agonists; D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D009579:Nitrobenzoates; D014404:Tubulin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D017239:Paclitaxel
references.citation: J Membr Biol. 2006 Jan;209(1):21-9
references.pmid: 16685598
references.citation: Apoptosis. 2006 Mar;11(3):327-36
references.pmid: 16520896
references.citation: Contrib Nephrol. 2006;152:142-160
references.pmid: 17065810
references.citation: Apoptosis. 2011 May;16(5):468-77
references.pmid: 21373935
references.citation: Curr Med Chem. 2009;16(1):66-93
references.pmid: 19149563
references.citation: Int J Biochem Cell Biol. 2013 Mar;45(3):672-83
references.pmid: 23270726
references.citation: Cytoskeleton (Hoboken). 2012 Mar;69(3):133-43
references.pmid: 22328323
references.citation: J Med Genet. 2009 Aug;46(8):497-510
references.pmid: 19505876
references.citation: Apoptosis. 2011 Feb;16(2):198-207
references.pmid: 21082356
references.citation: Arch Biochem Biophys. 2007 Jun 15;462(2):176-88
references.pmid: 17321483
references.citation: J Biol Chem. 2012 Mar 2;287(10):7803-11
references.pmid: 22262838
references.citation: Am J Physiol Cell Physiol. 2002 Oct;283(4):C1313-23
references.pmid: 12225994
references.citation: Biochem Pharmacol. 2012 Aug 1;84(3):292-302
references.pmid: 22617318
references.citation: Exp Biol Med (Maywood). 2011 Apr 1;236(4):483-91
references.pmid: 21454376
references.citation: Annu Rev Med. 1997;48:353-74
references.pmid: 9046968
references.citation: J Neurochem. 2012 Oct;123(1):1-13
references.pmid: 22845740
references.citation: J Physiol. 2007 Mar 15;579(Pt 3):717-28
references.pmid: 17204494
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1339-47
references.pmid: 17873007
references.citation: J Cell Physiol. 2013 May;228(5):991-1001
references.pmid: 23042559
references.citation: J Membr Biol. 2011 Mar;240(2):111-9
references.pmid: 21347611
references.citation: EMBO Rep. 2008 Jun;9(6):512-5
references.pmid: 18451877
references.citation: Neuroscience. 2010 May 5;167(2):298-311
references.pmid: 20144697
references.citation: Int J Physiol Pathophysiol Pharmacol. 2011;3(2):156-66
references.pmid: 21760973
references.citation: Biochem Pharmacol. 2012 Feb 1;83(3):324-34
references.pmid: 22108225
references.citation: Cell Death Differ. 2002 Jan;9(1):3-5
references.pmid: 11803369
references.citation: J Biol Chem. 2006 Dec 8;281(49):37566-75
references.pmid: 16950792
references.citation: J Cell Sci. 2008 Feb 1;121(Pt 3):290-7
references.pmid: 18198188
references.citation: Pflugers Arch. 2004 Jun;448(3):313-8
references.pmid: 15107996
references.citation: Eur J Pharmacol. 2010 Sep 1;641(2-3):88-95
references.pmid: 20522412
references.citation: Curr Med Chem. 2012;19(5):683-96
references.pmid: 22204341
references.citation: Cancer. 2000 Jun 1;88(11):2619-28
references.pmid: 10861441
references.citation: Am J Physiol Renal Physiol. 2006 Dec;291(6):F1113-22
references.pmid: 16926444
references.citation: Biochem Pharmacol. 2008 May 1;75(9):1706-16
references.pmid: 18359479
references.citation: J Cell Physiol. 2011 Oct;226(10):2516-26
references.pmid: 21792908
references.citation: Am J Physiol Cell Physiol. 2009 Dec;297(6):C1544-53
references.pmid: 19794143
references.citation: Acta Physiol (Oxf). 2006 May-Jun;187(1-2):27-42
references.pmid: 16734740
references.citation: Sheng Li Xue Bao. 2007 Aug 25;59(4):512-6
references.pmid: 17700971
references.citation: Cancer Chemother Pharmacol. 2011 Sep;68(3):553-7
references.pmid: 21713447
references.citation: J Biol Chem. 2012 Feb 24;287(9):6284-95
references.pmid: 22228768
references.citation: Histochem Cell Biol. 2012 Jun;137(6):763-76
references.pmid: 22371056
references.citation: Cell Physiol Biochem. 2011;28(6):1265-78
references.pmid: 22179014
references.citation: Cytometry. 1998 Jan 1;31(1):1-9
references.pmid: 9450519
references.citation: Cancers (Basel). 2011;3(2):2516-39
references.pmid: 23914299
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9487-92
references.pmid: 10900263