Pancreatic phospholipase A(2) via its receptor regulates the expression ofkey enzymes of phospholipid and sphingolipid metabolism

Citation
Ak. Mandal et al., Pancreatic phospholipase A(2) via its receptor regulates the expression ofkey enzymes of phospholipid and sphingolipid metabolism, FASEB J, 15(8), 2001, pp. NIL_24-NIL_38
Citations number
60
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
FASEB JOURNAL
ISSN journal
0892-6638 → ACNP
Volume
15
Issue
8
Year of publication
2001
Pages
NIL_24 - NIL_38
Database
ISI
SICI code
0892-6638(200106)15:8<NIL_24:PPAVIR>2.0.ZU;2-F
Abstract
Although the pancreatic secretory phospholipase A(2) (sPLA(2)IB) is conside red a digestive enzyme, it has several important, nonenzymatic, receptor-me diated functions. In this study, we demonstrate that via its receptor, sPLA (2)IB stimulates the expression of cytosolic PLA(2) (cPLA(2))-, cyclooxygen ase-2 (COX-2)-, Mg++-dependent neutral sphingomyelinase (NSMase)- and acid ceramidase (AC)- mRNAs in NIH 3T3 cells. Moreover, through its receptor, sP LA(2)IB also mediates the activation of cPLA(2) and p38 MAPK. We also found similar effects when the NIH 3T3 cells were treated with interleukin 1 bet a (IL-beta), fibroblast growth factor (FGF), and hepatocyte growth factor ( HGF) under identical conditions. These effects are not dependent on the cat alytic activity of sPLA(2)IB, as both heat- and chemically inactivated enzy me induced these effects. Although protein kinase C and p38 mitogen-activat ed protein kinases are critical for the sPLA(2) receptor-mediated stimulati on of expression of cytosolic PLA(2) and cyclooxygenase-2 mRNAs, respective ly, the activation of these kinases is not required for neutral sphingomyel inase and acid ceramidase mRNA expression. Our results, for the first time, raise the possibility that, via its receptor, sPLA(2)IB plays important ro les in the regulation of both phospholipid and sphingolipid metabolism.