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Transforming growth factor‐α stimulates prostaglandin generation through cytosolic phospholipase A 2 under the control of p11 in rat gastric epithelial cells
Author(s) -
Akiba Satoshi,
Hatazawa Ryo,
Ono Kyoko,
Hayama Misako,
Matsui Hirofumi,
Sato Takashi
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703637
Subject(s) - arachidonic acid , phospholipase a2 , tgf alpha , endocrinology , medicine , protein kinase c , prostaglandin , transforming growth factor , phospholipase , epidermal growth factor , biology , liberation , annexin a1 , chemistry , annexin , microbiology and biotechnology , biochemistry , kinase , receptor , flow cytometry , enzyme , in vitro
The regulatory effects of transforming growth factor (TGF)‐α on phospholipase A 2 (PLA 2 ) isozymes contributing to prostaglandin generation in rat gastric epithelial RGM1 cells were examined. Stimulation with TGF‐α for 24 h time‐dependently induced prostaglandin E 2 generation with an increase in cyclo‐oxygenase‐2 protein. The TGF‐α‐induced prostaglandin E 2 generation was suppressed by NS‐398, a cyclo‐oxygenase‐2 inhibitor. TGF‐α stimulated the activity and the protein synthesis of cytosolic PLA 2 (cPLA 2 ). A time‐dependent increase in cPLA 2 protein occurred in parallel with PGE 2 generation, which was inhibited by methyl arachidonyl fluorophosphonate (MAFP), a cPLA 2 inhibitor. However, no change in activity of secretory PLA 2 or Ca +2 ‐independent PLA 2 was observed in the TGF‐α‐stimulated cells. Stimulation with the Ca 2+ ionophore A23187 for 10 min induced MAFP‐sensitive arachidonic acid liberation. Interestingly, preincubation with TGF‐α for 24 h diminished A23187‐stimulated arachidonic acid liberation despite the increase in cPLA 2 protein. Under the conditions, TGF‐α was found to increase p11, an endogenous cPLA 2 suppressor, also known as annexin II light chain. The TGF‐α‐induced increase in p11 was suppressed by tyrphostin AG1478, an inhibitor of tyrosine kinase of epidermal growth factor receptor, which was also found to restore the inhibition by TGF‐α of A23187‐stimulated arachidonic acid liberation. However, TGF‐α did not alter protein levels of annexin II heavy chain. These results suggest that TGF‐α stimulates prostaglandin generation through an increase in cPLA 2 , the hydrolytic action of which may be under the control of p11.British Journal of Pharmacology (2000) 131 , 1004–1010; doi: 10.1038/sj.bjp.0703637