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BK‐induced cytosolic phospholipase A 2 expression via sequential PKC‐δ, p42/p44 MAPK, and NF‐κB activation in rat brain astrocytes
Author(s) -
Hsieh HsiLung,
Wu ChengYing,
Hwang TsongLong,
Yen MaoHsiung,
Parker Peter,
Yang ChuenMao
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20457
Subject(s) - rottlerin , mapk/erk pathway , protein kinase c , phospholipase c , microbiology and biotechnology , phosphorylation , cytosol , gq alpha subunit , transfection , blot , chemistry , signal transduction , biology , biochemistry , g protein , enzyme , gene
Bradykinin (BK), an inflammatory mediator, has been shown to induce cytosolic phospholipase A 2 (cPLA 2 ) expression implicating in inflammatory responses in various cell types. However, the detailed mechanisms underlying BK‐induced cPLA 2 expression in astrocytes remain unclear. RT‐PCR and Western blotting analysis showed that BK induced the expression of cPLA 2 mRNA and protein, which was inhibited by Hoe140, suggesting the involvement of B 2 BK receptors, confirmed by immunofluorescence staining using anti‐B 2 BK receptor antibody. BK‐induced cPLA 2 expression and phosphorylation of p42/p44 MAPK was attenuated by PD98059, indicating the involvement of MEK1/2‐p42/p44 MAPK in these responses. BK‐induced cPLA 2 expression might be due to the translocation of NF‐κB into nucleus which was inhibited by Hoe140, helenalin, and PD98059, implying the involvement of NF‐κB. Moreover, BK‐induced cPLA 2 expression was attenuated by rottlerin, suggesting that PKC‐δ might be involved in these responses. This hypothesis was supported by the transfection with a dominant negative plasmid of PKC‐δ significantly attenuated BK‐induced response. In addition, BK‐stimulated translocation of PKC‐δ from cytosol to membrane fraction was inhibited by rottlerin but not by PD98059, indicating that PKC‐δ might be an upstream component of p42/p44 MAPK. Accordingly, BK‐induced phosphorylation of p42/p44 MAPK was attenuated by rottlerin but not by helenalin. These results suggest that in RBA‐1 cells, BK‐induced cPLA 2 expression was sequentially mediated through activation of PKC‐δ, p42/p44 MAPK, and NF‐κB. Understanding the regulation of cPLA 2 expression induced by BK in astrocytes might provide a new therapeutic strategy of brain injury and inflammatory diseases. © 2005 Wiley‐Liss, Inc.