title: The AQP-3 water channel and the ClC-3 chloride channel coordinate the hypotonicity-induced swelling volume in nasopharyngeal carcinoma cells.
abstract: Cell volume regulation is a fundamental activity to maintain cell survival, and aquaporins and chloride channels play important roles in this process. However, the interactions between these channels are far from clear. In this study, the interactions between AQP-3 and ClC-3 were investigated in CNE-1 and CNE-2Z nasopharyngeal carcinoma cells, which are well and poorly differentiated, respectively. The correlation coefficient of AQP-3 and ClC-3 protein phylogenetic trees was 0.319. In CNE-1 cells, there are overlapping distributions of AQP-3 and ClC-3, mainly in the plasma membrane. This was confirmed by the co-immunoprecipitation of AQP-3 and ClC-3, showing that they could be interlinked and form complexes. AQP-3 over-expression had no significant effects on swelling-induced Cl(-) currents (ICl,swell); however, ICl,swell could be inhibited by aquaporin blockers, anti-AQP-3 antibodies and AQP-3-siRNAs. In addition, the AQP-3 expression was decreased by down-regulation of ClC-3 expression, indicating that ClC-3 can modulate the expression of AQP-3 proteins. The effects of aquaporin blockers, anti-AQP-3 antibodies and AQP-3 over-expression on ICl,swell in CNE-2Z cells were consistent with those in CNE-1 cells. In conclusion, AQP-3 and ClC-3 are functionally-related integral membrane channel proteins, and their interactions are involved in cell volume regulation in CNE-1 and CNE-2Z cells. The opening of ClC-3 transports Cl(-) across the cell membrane and then drives the efflux of water through AQP-3 channels and ion channels; AQP-3 may interact with ClC-3 in order to regulate the effluxes of chloride and water.
authors.affiliation: Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhf19841011@126.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Li
authors.affiliation: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Guang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.affiliation: Guangdong Key Laboratory for Bioactive Drugs Research and Department of Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: chenlixinw@sohu.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: twangliwei@jnu.edu.cn.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: C496027:AQP3 protein, human; D018118:Chloride Channels; C115376:ClC-3 channel; D034741:RNA, Small Interfering; D051400:Aquaporin 3
keywords: AQP-3; Aquaporins; Cell volume regulation; Chloride channels; ClC-3