Persulfate salts are broadly used as industrial chemicals and exposure to them causes occupational asthma, occupational rhinitis and contact dermatitis. However, the mechanisms underlying these toxic actions are not fully elucidated. Transient receptor potential (TRP) vanilloid 1 (V1), ankyrin 1 (A1) and melastatin 8 (M8) are non-selective cation channels preferentially expressing sensory neurons. These channels are known to be involved in respiratory and skin diseases. In the present study, we investigated the effects of sodium persulfate on these TRP channels. In wild-type mouse sensory neurons, persulfate evoked [Ca2+]i increases that were inhibited by removal of extracellular Ca2+ or blockers of TRPA1 but not by those of TRPV1 and TRPM8. Persulfate failed to evoke [Ca2+]i responses in neurons from TRPA1(-/-) mice, but did evoke them in neurons from TRPV1(-/-) mice. In HEK 293 cells expressing mouse TRPA1 (mTRPA1-HEK), persulfate induced [Ca2+]i increases. Moreover, in HEK 293 cells expressing mouse TRPV1 (mTRPV1-HEK), a high concentration of persulfate also evoked [Ca2+]i increases. Similar [Ca2+]i responses were observed in HEK 293 cells expressing human TRPA1 and human TRPV1. Current responses were also elicited by persulfate in mTRPA1- and mTRPV1-HEK. Analysis using mutated channels revealed that persulfate acted on electrophilic agonist-sensitive cysteine residues of TRPA1, and it indirectly activated TRPV1 due to the external acidification, because of the disappearance of [Ca2+]i responses in acid-insensitive mTRPV1 mutant. These results demonstrate that persulfate activates nociceptive TRPA1 and TRPV1 channels. It is suggested that activation of these nociceptive channels may be involved in respiratory and skin injuries caused by exposure to this industrial sulfur compound. Thus, selective TRPA1 and TRPV1 channel blockers may be effective to remedy persulfate-induced toxic actions.

中文翻译：

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通过过硫酸盐（一种工业硫化合物）鉴定具有毒性作用的分子靶标。

过硫酸盐被广泛用作工业化学品，接触过硫酸盐会引起职业性哮喘，职业性鼻炎和接触性皮炎。但是，尚未完全阐明这些毒性作用的潜在机制。瞬态受体电位（TRP）香草酸1（V1），锚蛋白1（A1）和褪黑素8（M8）是优先表达感觉神经元的非选择性阳离子通道。这些通道已知与呼吸道疾病和皮肤疾病有关。在本研究中，我们研究了过硫酸钠对这些TRP通道的影响。在野生型小鼠感觉神经元中，过硫酸盐诱发的[Ca2 +] i升高，其被细胞外Ca2 +或TRPA1阻滞剂的去除抑制，但未被TRPV1和TRPM8的阻滞剂抑制。过硫酸盐未能引起TRPA1（-/-）小鼠神经元中的[Ca2 +] i反应，但是确实在TRPV1（-/-）小鼠的神经元中引起了他们的注意。在表达小鼠TRPA1（mTRPA1-HEK）的HEK 293细胞中，过硫酸盐诱导的[Ca2 +] i增加。此外，在表达小鼠TRPV1（mTRPV1-HEK）的HEK 293细胞中，也引起了高浓度的过硫酸盐[Ca2 +] i的增加。在表达人TRPA1和人TRPV1的HEK 293细胞中观察到类似的[Ca2 +] i反应。mTRPA1-和mTRPV1-HEK中的过硫酸盐也引起了电流响应。使用突变通道进行的分析表明，过硫酸盐作用于TRPA1的亲电激动剂敏感半胱氨酸残基，由于对酸不敏感的mTRPV1突变体中[Ca2 +] i反应的消失，它由于外部酸化而间接激活了TRPV1。这些结果表明，过硫酸盐可激活伤害性TRPA1和TRPV1通道。建议这些伤害性通道的激活可能与暴露于这种工业硫化合物引起的呼吸道和皮肤损伤有关。因此，选择性的TRPA1和TRPV1通道阻滞剂可能有效纠正过硫酸盐诱导的毒性作用。