Rottlerin, a specific inhibitor of protein kinase C-delta, impedes barrier repair response by increasing intracellular free calcium

Bong K. Ahn, Se K. Jeong, Hee S. Kim, Ki J. Choi, Jung T. Seo, Eung H. Choi, Sung K. Ahn, Seung H. Lee

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Abstract

Several signals have been suggested in maintaining skin barrier homeostasis, but epidermal calcium ions are currently thought to be a main signaling factor. It is not clear, however, exactly how an intracellular calcium level decreases in response to the loss of an extracellular calcium gradient. In this study, we investigated the effects of several broad-type and isozyme-specific protein kinase C (PKC) inhibitors on epidermal permeability barrier recovery. Topical application of chelerythrine chloride, a broad-type PKC inhibitor, and rottlerin, a PKCδ-specific inhibitor, significantly impeded the barrier recovery rate at 3 and 6 hours after barrier disruption. A significant decrease in the number and secretion of lamellar bodies was also observed at the inhibitor-treated site. Calcium ion-capture cytochemistry showed that the epidermal calcium gradient was rapidly reformed in inhibitor-treated skin, though recovery of the corresponding barrier function was not observed. In cultured keratinocytes treated with either inhibitor, increased intracellular calcium did not return to the baseline concentration after extracellular calcium decreased. These results suggest that PKC inhibitors, especially a PKCδ-specific inhibitor, delay barrier recovery by affecting the intracellular calcium concentration after a loss of the extracellular calcium gradient. Furthermore, PKCδ is important in controlling a decrease in intracellular calcium concentration.

Original languageEnglish
Pages (from-to)1348-1355
Number of pages8
JournalJournal of Investigative Dermatology
Volume126
Issue number6
DOIs
Publication statusPublished - 2006 Jun 1

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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