Psoralens activate and photosensitize Transient Receptor Potential channels Ankyrin type 1 (TRPA1) and Vanilloid type 1 (TRPV1)
Psoralens activate and photosensitize Transient Receptor Potential channels Ankyrin type 1 (TRPA1) and Vanilloid type 1 (TRPV1)
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DOI：
10.1002/ejp.1654
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发表时间：
2020-09-23
影响因子：
3.6
通讯作者：
Reeh, Peter W.
中科院分区：
文献类型：
--
作者：
Babes, Alexandru;Kichko, Tatjana I.;Reeh, Peter W.
背景 PUVA（补骨脂素 UVA）疗法用于治疗多种皮肤病，如白癜风、银屑病、湿疹和蕈样肉芽肿，但常常伴随光毒性，导致灼痛、瘙痒和红斑。方法 我们结合使用钙和活性氧 (ROS) 成像、膜片钳和神经肽释放测量来研究涉及疼痛和瘙痒信号传导的某些离子通道是否可能导致 PUVA 的这些不良反应。结果临床使用的补骨脂素衍生物8-甲氧基补骨脂素（8-MOP）和5-甲氧基补骨脂素在生理相关浓度下能够激活和光敏化两个重组thermoTRP（温度门控瞬时受体电位）离子通道TRPA1（瞬时受体电位锚蛋白1型）和TRPV1（瞬时受体电位香草酸1型）。 8-MOP 通过 UVA 光增强 ROS 产生，并且 8-MOP 对 TRPA1 的影响可以通过抗氧化剂 N-乙酰半胱氨酸和去除通道 N 末端结构域中的关键半胱氨酸残基来消除。天然表达的小鼠 TRPA1 和 TRPV1 均有助于 8-MOP 对培养的初级传入神经元的光敏化，而这种补骨脂素衍生物的直接神经元激活主要依赖于 TRPV1。 TRPA1 和 TRPV1 在很大程度上参与控制 8-MOP 诱导的小鼠气管神经肽释放。结论 总而言之，我们的结果可以更好地了解 PUVA 患者报告的光毒性，并指出一种可能的治疗方法来减轻与该疗法相关的不良反应。意义我们的工作提供了在 PUVA（补骨脂素 UVA）治疗期间，thermoTRP 通道 TRPA1 和 TRPV1 参与外周伤害感受器的激活和光敏化的证据。
Background PUVA (psoralen UVA) therapy is used to treat a variety of skin conditions, such as vitiligo psoriasis, eczema and mycosis fungoides, but it is frequently accompanied by phototoxicity leading to burning pain, itch and erythema. Methods We used a combination of calcium and reactive oxygen species (ROS) imaging, patch clamp and neuropeptide release measurement to investigate whether certain ion channels involved in pain and itch signalling could be responsible for these adverese effects of PUVA. Results Clinically used psoralen derivatives 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen at physiologically relevant concentrations were able to activate and photosensitize two recombinant thermoTRP (temperature-gated Transient Receptor Potential) ion channels, TRPA1 (Transient Receptor Potential Ankyrin type 1) and TRPV1 (Transient Receptor Potential Vanilloid type 1). 8-MOP enhanced ROS production by UVA light, and the effect of 8-MOP on TRPA1 could be abolished by the antioxidant N-acetyl cysteine and by removal of critical cysteine residues from the N-terminus domain of the channel. Natively expressed mouse TRPA1 and TRPV1 both contribute to photosensitization of cultured primary afferent neurons by 8-MOP, while direct neuronal activation by this psoralen-derivative is mainly dependent on TRPV1. Both TRPA1 and TRPV1 are to a large extent involved in controlling 8-MOP-induced neuropeptide release from mouse trachea. Conclusions Taken together our results provide a better understanding of the phototoxicity reported by PUVA patients and indicate a possible therapeutic approach to alleviate the adverse effects associated with this therapy. Significance Our work provides evidence for the involvement of thermoTRP channels TRPA1 and TRPV1 in the activation and photosensitization of peripheral nociceptors during PUVA (Psoralen UVA) therapy.