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Protein kinase Cδ‐mediated CREB activation regulates ghrelin‐induced cyclooxygenase‐2 expression and prostaglandin E2 production in human colonic epithelial cells
Author(s) -
Zhao Dezheng
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21355
Subject(s) - creb , prostaglandin e2 , cyclooxygenase , ghrelin , microbiology and biotechnology , chemistry , protein kinase c , prostaglandin , protein kinase a , kinase , medicine , cancer research , endocrinology , biology , enzyme , transcription factor , biochemistry , gene , receptor
Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone release and appetite. Our recent study showed that ghrelin could stimulate protein kinase C‐mediated activation of nuclear factor‐κB (NF‐κB) and interleukin‐8 secretion in human colonic epithelial cells transfected with a functional ghrelin receptor. In the present study, the effect of ghrelin stimulation on cyclooxygenese‐2 expression and prostaglandin E2 production was examined. The data indicate that ghrelin significantly increased the levels of cyclooxygenase‐2 (COX‐2) protein as well as its promoter activity, which leaded to profound increase in prostaglandin E2 secretion. In order to examine the involvement of NF‐κB and cAMP responsive element‐binding protein (CREB) in this response, the NF‐κB inhibitory protein IκBα or a dominant negative mutant of CREB was co‐transfected into cells and the data show that transfection of either IκBα or DN‐CREB significantly attenuated ghrelin‐induced COX‐2 expression. Moreover ghrelin stimulated phosphorylation of CREB, which was mediated primarily via protein kinase Cδ activation. Furthermore, inhibition of PKCδ function significantly attenuated ghrelin‐induced COX‐2 expression. In addition, ghrelin stimulates phosphorylation of PKCδ. Together, these results indicate that in addition to NF‐κB, protein kinase Cδ‐mediated CREB activation plays an important role in the cellular responses of ghrelin. J. Cell. Biochem. 102: 1245–1255, 2007. © 2007 Wiley‐Liss, Inc.