Protein Kinase C-α Coordinately Regulates Cytosolic Phospholipase A2Activity and the Expression of Cyclooxygenase-2 through Different Mechanisms in Mouse Keratinocytes
| العنوان: | Protein Kinase C-α Coordinately Regulates Cytosolic Phospholipase A2Activity and the Expression of Cyclooxygenase-2 through Different Mechanisms in Mouse Keratinocytes |
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| المؤلفون: | Hui Qin Wang, Robert C. Smart, Robert Langenbach, Howard F. Tiano, Michael P. Kim |
| المصدر: | Molecular Pharmacology. 59:860-866 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Keratinocytes, Protein Kinase C-alpha, Prostaglandin, Mice, Transgenic, Biology, Dinoprostone, Phospholipases A, Mice, chemistry.chemical_compound, Cytosol, medicine, Animals, Protein Isoforms, Enzyme Inhibitors, Phosphorylation, Promoter Regions, Genetic, Protein kinase A, Cells, Cultured, Phospholipids, Protein Kinase C, Protein kinase C, Skin, Inflammation, Mitogen-Activated Protein Kinase Kinases, Pharmacology, Arachidonic Acid, integumentary system, CCAAT-Enhancer-Binding Protein-beta, Molecular biology, Isoenzymes, Keratin 5, medicine.anatomical_structure, chemistry, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, Phorbol, Keratins, Tetradecanoylphorbol Acetate, Molecular Medicine, Arachidonic acid, Keratinocyte, Signal Transduction |
| الوصف: | Transgenic mice (K5-PKC alpha) in which the keratin 5 promoter directs the expression of protein kinase C-alpha (PKC alpha) to epidermal keratinocytes display a 10-fold increase in PKC alpha protein in their epidermis and alterations in phorbol ester-induced cutaneous inflammation [J Cell Science 1999;112:3497-3506]. In the current study, we have used these K5-PKC alpha mice to examine the role of PKC alpha in keratinocyte phospholipid metabolism/eicosanoid production and cutaneous inflammation. Primary keratinocytes from wild-type and transgenic mice were prelabeled in culture with [(3)H]arachidonic acid (AA) and subsequently treated with TPA. Compared with wild-type keratinocytes, K5-PKC alpha keratinocytes displayed a 2-fold increase in AA release. TPA treatment resulted in the phosphorylation of cPLA(2). PKC inhibitors GF-109203X or H7, but not mitogen-activated protein/extracellular signal-regulated protein kinase (MEK) inhibitor PD 98059, could inhibit phosphorylation and AA release. Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of K5-PKC alpha mice resulted in a 5-fold increase in epidermal COX-2 induction and a 2- to 3-fold increase in prostaglandin (PG) E(2) levels above that observed in TPA-treated wild-type mice. PD 98059, GF-109203X, or H7 could block cyclooxygenase-2 (COX-2) induction by TPA. Because C/EBP beta, a basic leucine zipper transcription factor, can be activated via a PKC alpha/mitogen-activated protein kinase pathway and can influence COX-2 expression, we examined whether C/EBP beta is involved in TPA-induced epidermal COX-2 expression. TPA-induced COX-2 expression was similar in C/EBP beta nullizygous and wild-type mice. In summary, our results indicate that epidermal PKC alpha coordinately regulates cPLA(2) activity and COX-2 expression resulting in increased levels of AA and PGE(2). Furthermore, PKC alpha-induced AA release and cPLA(2) phosphorylation are independent of MEK, whereas PKC alpha-induced COX-2 expression and PGE(2) production are MEK-dependent and C/EBP beta-independent events. |
| تدمد: | 1521-0111 0026-895X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e447351bdda7ba7957e7ea90cf8c0b60Test https://doi.org/10.1124/mol.59.4.860Test |
| رقم الانضمام: | edsair.doi.dedup.....e447351bdda7ba7957e7ea90cf8c0b60 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210111 0026895X |
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