Mao Jianwen, Chen Lixin, Xu Bin, Wang Lijing, Wang Weizhang, Li Ming, Zheng Min, Li Hongzhi, Guo Jiao, Li Weidong, Jacob Tim J C, Wang Liwei
Institute of Basic Medical Sciences and Department of Biology, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangdong, China.
Biochem Pharmacol. 2009 Jan 15;77(2):159-68. doi: 10.1016/j.bcp.2008.10.009. Epub 2008 Oct 15.
The activation of volume-activated chloride Cl(-) channels has been implicated to play important roles in modulating cell cycle and cell migration. The aim of this study was to determine whether volume-activated Cl(-) channels are involved in cell-cycle-dependent regulation of cell migration in HeLa cells. Using techniques including cell-cycle synchronization, transwell migration assays and the patch-clamp technique, we demonstrate in this study that both the expression of volume-activated chloride current (I(Cl,vol)) and the potential of cell migration are cell-cycle-dependent; specifically, these events were high in G(0)/G(1) phase, low in S phase, and medium in G(2)/M phase. Moreover, the mean density of I(Cl,vol) was positively correlated to the rate of cell migration during cell-cycle progression. Additionally, endogenous suppression of I(Cl,vol) by transfecting cells with ClC-3 antisense oligonucleotides arrested cells in S phase and slowed cell migration. Collectively, our results suggest that volume-activated Cl(-) channels contribute to the cell-cycle-dependent regulation of cell migration.
容积激活氯(Cl⁻)通道的激活被认为在调节细胞周期和细胞迁移中发挥重要作用。本研究的目的是确定容积激活Cl⁻通道是否参与HeLa细胞中细胞迁移的细胞周期依赖性调节。通过使用包括细胞周期同步化、Transwell迁移实验和膜片钳技术在内的技术,我们在本研究中证明,容积激活氯电流(I(Cl,vol))的表达和细胞迁移潜力均呈细胞周期依赖性;具体而言,这些事件在G(0)/G(1)期较高,在S期较低,在G(2)/M期中等。此外,在细胞周期进程中,I(Cl,vol)的平均密度与细胞迁移速率呈正相关。另外,用ClC-3反义寡核苷酸转染细胞对内源性I(Cl,vol)的抑制使细胞停滞在S期并减缓细胞迁移。总体而言,我们的结果表明容积激活Cl⁻通道有助于细胞迁移的细胞周期依赖性调节。