Microsoft Word - Cao X et al, TRPV3 and intracellular proton, Revision May 30, 2012

Intracellular proton‐mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes Xu Cao, Fan Yang, Jie Zheng and KeWei Wang Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center; Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA 95616; USA; Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, 38 Xueyuan Road, Beijing 100191, China Running title: Proton activation of TRPV3 To whom correspondence should be addressed: KeWei Wang ([email protected]), (8610) 82805065; and Jie Zheng ([email protected]), 530‐7521241 Capsule: Background: Little is known about how alpha hydroxyl acids (AHAs) widely cause exfoliation to expose fresh skin cells. Results: TRPV3 channel in keratinocytes is potently activated by intracellular acidification induced by glycolic acid. Conclusion: TRPV3‐mediated proton‐sensing and cell death in keratinocytes may serve as a molecular basis for the cosmetic use of AHAs. Significance: We describe a novel mechanism by which TRPV3 is activated by intracellular protons.