Evidence of nuclear PKC/MAP-kinase cascade in guinea pig model of epidermal hyperproliferation.
In order to delineate the biochemical events in the nuclear compartment of an in vivo proliferating epidermis, we produced a model of hyperproliferative epidermis by topical application of docosahexaenoic acid (22:6n-3) on guinea pig skin. Employing this model we demonstrated: (i) that protein kinase C (PKC)-a and atypical PKC-zeta are the two major PKC isozymes in the normal epidermal nuclear membrane, in contrast to PKC-alpha and PKC-beta in the epidermal plasma membrane; (ii) that topical application of docosahexaenoic acid induced epidermal hyperproliferation and enhanced total nuclear PKC, particularly nuclear PKC-alpha and the atypical PKC-zeta isozymes. The increase in the nuclear PKC isozymes paralleled a marked increase in the expression of nuclear mitogen-activated protein-kinase. These data suggest that epidermal hyperproliferative activity is accompanied by the upregulation of nuclear PKC/mitogen-activated protein-kinase signaling pathway.
Mani
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Department of Dermatology, University of California, Davis 95616, USA.
Iversen
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Ziboh
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D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004817:Epidermis / Q000201:enzymology* / Q000473:pathology*; D006168:Guinea Pigs; D007527:Isoenzymes / Q000096:biosynthesis; D008041:Linoleic Acids / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000096:biosynthesis*; D015854:Up-Regulation
D007527:Isoenzymes; D008041:Linoleic Acids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases