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Archives of Dermatological Research
Published in: Archives of Dermatological Research 2/2007

01-05-2007 | Original Paper

Activation of PKCδ and p38δ MAPK during okadaic acid dependent keratinocyte apoptosis

Authors: Catherine A. Kraft, Tatiana Efimova, Richard L. Eckert

Published in: Archives of Dermatological Research | Issue 2/2007

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Abstract

There is substantial interest in identifying agents that differentially activate keratinocyte differentiation versus apoptosis. Okadaic acid (OA) is a tumor promoter in mouse skin that also stimulates apoptosis of murine keratinocytes. OA also enhances human keratinocyte differentiation; however, the impact of OA treatment on apoptosis in these cells has not been examined. We show that OA promotes normal human keratinocyte apoptosis as evidenced by increased accumulation of cells having sub-G1/S DNA content, decreased mitochondrial integrity, increased annexin V binding, increased cytoplasmic cytochrome c level, and increased procaspase 3 and PARP cleavage. Cyclin A, cyclin D1, cdk2, cdk4, p53 and p21 levels are reduced. These changes are associated with release of the PKCδ catalytic domain and increased phosphorylation of PKCδ-T505-responses consistent with PKCδ activation. In contrast, phosphorylation of PKCδ-Y311 is not increased. The apoptotic response is enhanced in OA treated cells in the presence of p38δ, a PKCδ target. OA treatment selectively activated p38δ, and OA-dependent apoptosis is not inhibited by treatment with the p38α/β inhibitor, SB203580. These findings are consistent with the idea that the response is mediated by p38δ. Our data indicate that OA is an agent that regulates both keratinocyte differentiation and apoptosis, and that this regulation is mediated via activation of a PKCδ/p38δ signaling cascade.
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Metadata
Title
Activation of PKCδ and p38δ MAPK during okadaic acid dependent keratinocyte apoptosis
Authors
Catherine A. Kraft
Tatiana Efimova
Richard L. Eckert
Publication date
01-05-2007
Publisher
Springer-Verlag
Published in
Archives of Dermatological Research / Issue 2/2007
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-006-0727-4

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