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学科主题: 基础医学
题名:
Intracellular Proton-mediated Activation of TRPV3 Channels Accounts for the Exfoliation Effect of alpha-Hydroxyl Acids on Keratinocytes
作者: Cao, Xu1,2; Yang, Fan1; Zheng, Jie1; Wang, Kewei2,3
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2012-07-27
DOI: 10.1074/jbc.M112.364869
卷: 287, 期:31, 页:25905-25916
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: RECEPTOR POTENTIAL CHANNELS ; CAPSAICIN RECEPTOR ; 2-AMINOETHOXYDIPHENYL BORATE ; GLYCOLIC ACID ; ION CHANNELS ; NOCICEPTIVE NEURONS ; COMMON ACTIVATOR ; CHORDA TYMPANI ; CATION CHANNEL ; HAIR-GROWTH
英文摘要:

alpha-Hydroxyl acids (AHAs) from natural sources act as proton donors and topical compounds that penetrate skin and are well known in the cosmetic industry for their use in chemical peels and improvement of the skin. However, little is known about how AHAs cause exfoliation to expose fresh skin cells. Here we report that the transient receptor potential vanilloid 3 (TRPV3) channel in keratinocytes is potently activated by intracellular acidification induced by glycolic acid. Patch clamp recordings and cell death assay of both human keratinocyte HaCaT cells and TRPV3-expressing HEK-293 cells confirmed that intracellular acidification led to direct activation of TRPV3 and promoted cell death. Site-directed mutagenesis revealed that an N-terminal histidine residue, His-426, known to be involved in 2-aminoethyl diphenylborinate-mediated TRPV3 activation, is critical for sensing intracellular proton levels. Taken together, our findings suggest that intracellular protons can strongly activate TRPV3, and TRPV3-mediated proton sensing and cell death in keratinocytes may serve as a molecular basis for the cosmetic use of AHAs and their therapeutic potential in acidic pH-related skin disorders.

语种: 英语
所属项目编号: R01NS072377 ; 30970919 ; B07001
项目资助者: National Institutes of Health ; National Science Foundation of China ; Ministry of Education of China 111 Project China ; China Scholarship Council
WOS记录号: WOS:000306916300019
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55981
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Univ Calif Davis, Sch Med, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
2.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Neurosci Res Inst, Beijing 100191, Peoples R China
3.Peking Univ, Dept Mol & Cellular Pharmacol, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Cao, Xu,Yang, Fan,Zheng, Jie,et al. Intracellular Proton-mediated Activation of TRPV3 Channels Accounts for the Exfoliation Effect of alpha-Hydroxyl Acids on Keratinocytes[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(31):25905-25916.
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