PubMed 24026363

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC3 , ClvC4

Title: The ClC-3 chloride channel associated with microtubules is a target of paclitaxel in its induced-apoptosis.

Authors: Haifeng Zhang, Huarong Li, Lili Yang, Zhiqin Deng, Hai Luo, Dong Ye, Zhiquan Bai, Linyan Zhu, Wencai Ye, Liwei Wang, Lixin Chen

Journal, date & volume: Sci Rep, 2013 , 3, 2615

PubMed link:

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.