Document Detail


Intracellular proton-mediated activation of TRPV3 channels accounts for the exfoliation effect of α-hydroxyl acids on keratinocytes.
MedLine Citation:
PMID:  22679014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
α-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.
Authors:
Xu Cao; Fan Yang; Jie Zheng; Kewei Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-10-11     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25905-16     Citation Subset:  IM    
Affiliation:
Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Amino Acid Substitution
Boron Compounds / pharmacology
Cell Line
Cell Survival / drug effects
Cosmetics / pharmacology
Glycolates / pharmacology*
Humans
Hydrogen-Ion Concentration
Keratinocytes / drug effects*,  metabolism,  physiology
Keratolytic Agents / pharmacology*
Membrane Potentials / drug effects
Molecular Sequence Data
Mutagenesis, Site-Directed
Patch-Clamp Techniques
Protein Structure, Tertiary
Skin / cytology,  drug effects
TRPV Cation Channels / agonists,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 NS072377/NS/NINDS NIH HHS; R01NS072377/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/2-aminoethyl diphenylborinate; 0/Boron Compounds; 0/Cosmetics; 0/Glycolates; 0/Keratolytic Agents; 0/TRPV Cation Channels; 0/TRPV3 protein, human; 79-14-1/glycolic acid
Comments/Corrections

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