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
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.