NAD(P)H Oxidase-derived H2O2 Signals Chloride Channel Activation in Cell Volume Regulation and Cell Proliferation*
NAD(P)H Oxidase-derived H2O2 Signals Chloride Channel Activation in Cell Volume Regulation and Cell Proliferation*
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DOI：
10.1074/jbc.c400020200
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发表时间：
2004-04
影响因子：
4.8
通讯作者：
D. Varela;F. Simon;A. Riveros;F. Jørgensen;A. Stutzin
中科院分区：
文献类型：
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作者：
D. Varela;F. Simon;A. Riveros;F. Jørgensen;A. Stutzin
在许多细胞类型中，细胞肿胀触发Cl-通道（体积敏感性向外整流（VSOR）Cl-通道）的激活。随后的调节性容量减少被认为是这些通道的主要功能。然而，与体积敏感性Cl-通道具有相同功能特性的Cl-通道已被证明参与其他生理过程，包括细胞增殖和凋亡，从而提出了它们的生理作用和参与其激活的信号转导途径的问题。在这里，我们报告，外源性应用过氧化氢引起VSOR Cl-通道激活。此外，发现这些通道的激活与NAD（P）H氧化酶活性偶联。此外，表皮生长因子，已知增加过氧化氢的生产，激活氯离子通道的性质相同的膨胀敏感性氯离子通道。结论：NAD（P）H氧化酶衍生的H2 O2是介导这些普遍表达的阴离子通道在各种生理条件下激活的常见信号转导分子。
Cellular swelling triggers the activation of Cl– channels (volume-sensitive outwardly rectifying (VSOR) Cl– channels) in many cell types. Ensuing regulatory volume decrease has been considered the primary function of these channels. However, Cl– channels, which share functional properties with volume-sensitive Cl– channels, have been shown to be involved in other physiological processes, including cell proliferation and apoptosis, raising the question of their physiological roles and the signal transduction pathways involved in their activation. Here we report that exogenously applied H2O2 elicited VSOR Cl– channel activation. Furthermore, activation of these channels was found to be coupled to NAD(P)H oxidase activity. Also, epidermal growth factor, known to increase H2O2 production, activated Cl– channels with properties identical to swelling-sensitive Cl– channels. It is concluded that NAD(P)H oxidase-derived H2O2 is the common signal transducing molecule that mediates the activation of these ubiquitously expressed anion channels under a variety of physiological conditions.