Integrative Physiology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 5650871, Osaka, Japan.
Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamada-oka, Suita 5650871, Osaka, Japan.
Int J Mol Sci. 2021 Mar 5;22(5):2620. doi: 10.3390/ijms22052620.
The voltage-gated proton channel, Hv1, also termed VSOP, was discovered in 2006. It has long been suggested that proton transport through voltage-gated proton channels regulate reactive oxygen species (ROS) production in phagocytes by counteracting the charge imbalance caused by the activation of NADPH oxidase. Discovery of Hv1/VSOP not only confirmed this process in phagocytes, but also led to the elucidation of novel functions in phagocytes. The compensation of charge by Hv1/VSOP sustains ROS production and is also crucial for promoting Ca influx at the plasma membrane. In addition, proton extrusion into neutrophil phagosomes by Hv1/VSOP is necessary to maintain neutral phagosomal pH for the effective killing of bacteria. Contrary to the function of Hv1/VSOP as a positive regulator for ROS generation, it has been revealed that Hv1/VSOP also acts to inhibit ROS production in neutrophils. Hv1/VSOP inhibits hypochlorous acid production by regulating degranulation, leading to reduced inflammation upon fungal infection, and suppresses the activation of extracellular signal-regulated kinase (ERK) signaling by inhibiting ROS production. Thus, Hv1/VSOP is a two-way player regulating ROS production. Here, we review the functions of Hv1/VSOP in neutrophils and discuss future perspectives.
电压门控质子通道 Hv1（也称为 VSOP）于 2006 年被发现。长期以来，人们一直认为通过电压门控质子通道的质子转运可以通过抵消 NADPH 氧化酶激活引起的电荷失衡来调节吞噬细胞中的活性氧（ROS）产生。Hv1/VSOP 的发现不仅证实了吞噬细胞中的这一过程，而且还阐明了吞噬细胞中的新功能。Hv1/VSOP 通过补偿电荷来维持 ROS 的产生，对于促进质膜 Ca2+内流也至关重要。此外，通过 Hv1/VSOP 将质子逐出中性粒细胞吞噬体对于维持吞噬体的中性 pH 以有效杀死细菌是必要的。与 Hv1/VSOP 作为 ROS 生成的正调节剂的功能相反，已经揭示 Hv1/VSOP 还可以抑制中性粒细胞中的 ROS 生成。Hv1/VSOP 通过调节脱粒来抑制次氯酸的产生，从而减少真菌感染时的炎症反应，并通过抑制 ROS 产生来抑制细胞外信号调节激酶（ERK）信号的激活。因此，Hv1/VSOP 是一种双向调节 ROS 产生的分子。在这里，我们综述了 Hv1/VSOP 在中性粒细胞中的功能，并讨论了未来的研究方向。
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