Hu Hongzhen, Bandell Michael, Petrus Matt J, Zhu Michael X, Patapoutian Ardem
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
Nat Chem Biol. 2009 Mar;5(3):183-90. doi: 10.1038/nchembio.146. Epub 2009 Feb 8.
Zinc is an essential biological trace element. It is required for the structure or function of over 300 proteins, and it is increasingly recognized for its role in cell signaling. However, high concentrations of zinc have cytotoxic effects, and overexposure to zinc can cause pain and inflammation through unknown mechanisms. Here we show that zinc excites nociceptive somatosensory neurons and causes nociception in mice through TRPA1, a cation channel previously shown to mediate the pungency of wasabi and cinnamon through cysteine modification. Zinc activates TRPA1 through a unique mechanism that requires zinc influx through TRPA1 channels and subsequent activation via specific intracellular cysteine and histidine residues. TRPA1 is highly sensitive to intracellular zinc, as low nanomolar concentrations activate TRPA1 and modulate its sensitivity. These findings identify TRPA1 as an important target for the sensory effects of zinc and support an emerging role for zinc as a signaling molecule that can modulate sensory transmission.
锌是一种必需的生物微量元素。它是300多种蛋白质的结构或功能所必需的，并且其在细胞信号传导中的作用越来越受到认可。然而，高浓度的锌具有细胞毒性作用，过度暴露于锌会通过未知机制导致疼痛和炎症。在这里，我们表明锌会刺激伤害性体感神经元，并通过TRPA1在小鼠中引起伤害感受，TRPA1是一种阳离子通道，先前已证明它通过半胱氨酸修饰介导芥末和肉桂的辛辣味。锌通过一种独特的机制激活TRPA1，该机制需要锌通过TRPA1通道流入并随后通过特定的细胞内半胱氨酸和组氨酸残基激活。TRPA1对细胞内锌高度敏感，因为低纳摩尔浓度就能激活TRPA1并调节其敏感性。这些发现确定TRPA1是锌感觉效应的重要靶点，并支持锌作为一种可以调节感觉传递的信号分子的新作用。
