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

Authors
 Bong K Ahn  ;  Se K Jeong  ;  Hee S Kim  ;  Ki J Choi  ;  Jung T Seo  ;  Eung H Choi  ;  Sung K Ahn  ;  Seung H Lee 
Citation
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.126(6) : 1348-1355, 2006 
Journal Title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN
 0022-202X 
Issue Date
2006
MeSH
Acetophenones/pharmacology* ; Animals ; Benzopyrans/pharmacology* ; Calcium/analysis ; Calcium/metabolism* ; Cells, Cultured ; Epidermis/chemistry ; Epidermis/drug effects* ; Epidermis/metabolism ; Isoenzymes/antagonists & inhibitors ; Lipids/analysis ; Lipids/biosynthesis ; Male ; Mice ; Mice, Hairless ; Protein Kinase C-delta/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Wound Healing/drug effects*
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 PKCdelta-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 PKCdelta-specific inhibitor, delay barrier recovery by affecting the intracellular calcium concentration after a loss of the extracellular calcium gradient. Furthermore, PKCdelta is important in controlling a decrease in intracellular calcium concentration.
Files in This Item:
T200600077.pdf Download
DOI
10.1038/sj.jid.5700244
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Lee, Seung Hun(이승헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108844
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