Involvement of Transient Receptor Potential Cation Channel Member A1 activation in the irritation and pain response elicited by skin-lightening reagent hydroquinone.
Involvement of Transient Receptor Potential Cation Channel Member A1 activation in the irritation and pain response elicited by skin-lightening reagent hydroquinone.
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瞬态受体电位阳离子通道成员 A1 激活参与亮肤试剂氢醌引起的刺激和疼痛反应
DOI：
10.1038/s41598-017-07651-5
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发表时间：
2017-08-08
影响因子：
4.6
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Tai Y;Wang C;Wang Z;Liang Y;Du J;He D;Fan X;Jordt SE;Liu B
对苯二酚（HQ）是最常用和有效的皮肤美白产品之一，用于治疗皮肤色素沉着过度疾病，包括炎症后色素沉着过度，黄褐斑和日光性雀斑。HQ还广泛用于皮肤美白的化妆品中。然而，HQ治疗会引起严重的皮肤刺激，这是一种仍然知之甚少的副作用。在这里，我们证明，HQ是外周刺激受体瞬时受体电位（TRP）阳离子通道成员A1（TRPA 1）的激活剂。HQ未能激活TRPV 1、TRPV 4或TRPM 8。HQ诱导的TRPA 1激活依赖于通道蛋白N-末端内的必需氧化还原敏感的半胱氨酸和赖氨酸残基。HQ引起的Ca 2+内流在一个亚群的小鼠感觉神经元敏感的TRPA 1激动剂，芥子油。HQ诱导的神经元反应显着降低TRPA 1抑制剂，并减少从Trpa 1缺陷小鼠分离的神经元。在小鼠中，足底注射临床相关浓度的HQ引起急性疼痛和持续的机械性痛觉过敏，这几乎完全被TRPA 1抑制剂消除。这些发现将TRPA 1确定为HQ的分子靶点，并为HQ诱导的皮肤刺激机制提供了见解。这些发现还表明，选择性TRPA 1拮抗剂可能有助于抵消HQ诱导的皮肤刺激。
Hydroquinone (HQ) is one of the most frequently used and effective skin-lightening products to treat skin hyperpigmentation disorders, including postinflammatory hyperpigmentation, melasma and solar lentigines. HQ is also widely used in cosmetic products for skin whitening. However, HQ treatment can evoke substantial skin irritation, a side effect that remains poorly understood. Here we demonstrate that HQ is an activator of the peripheral irritant receptor transient receptor potential (TRP) cation channel member A1 (TRPA1). HQ failed to activate TRPV1, TRPV4 or TRPM8. HQ-induced TRPA1 activation was dependent on essential redox-sensitive cysteine and lysine residues within N-terminus of channel protein. HQ elicited Ca2+ influx in a subpopulation of mouse sensory neurons sensitive to the TRPA1 agonist, mustard oil. HQ-induced neuronal responses were significantly reduced by TRPA1 inhibitors, and reduced in neurons isolated from Trpa1-deficient mice. In mice, intraplantar injection of HQ at clinically relevant concentrations elicited both acute pain and persistent mechanical hyperalgesia which were almost completely abolished by TRPA1 inhibitors. These findings identify TRPA1 as a molecular target for HQ and provide insights into the mechanism of HQ-induced skin irritation. These findings also suggest that selective TRPA1 antagonists may be useful to counteract HQ-induced skin irritation.
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影响因子：
7.4
作者：
Liu B;Fan L;Balakrishna S;Sui A;Morris JB;Jordt SE
通讯作者：
Jordt SE
TRPV4和TRPA1的小分子双抑制剂，用于炎症和疼痛的衰减。
影响因子：
4.6
作者：
Kanju P;Chen Y;Lee W;Yeo M;Lee SH;Romac J;Shahid R;Fan P;Gooden DM;Simon SA;Spasojevic I;Mook RA;Liddle RA;Guilak F;Liedtke WB
通讯作者：
Liedtke WB
锌激活损伤感应TRPA1离子通道。
影响因子：
14.8
作者：
Hu, Hongzhen;Bandell, Michael;Petrus, Matt J.;Zhu, Michael X.;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
4.6
作者：
Kistner K;Siklosi N;Babes A;Khalil M;Selescu T;Zimmermann K;Wirtz S;Becker C;Neurath MF;Reeh PW;Engel MA
通讯作者：
Engel MA
影响因子：
3.3
作者：
Miura S;Takahashi K;Imagawa T;Uchida K;Saito S;Tominaga M;Ohta T
通讯作者：
Ohta T