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Pancreatic phospholipase A 2 via its receptor regulates the expression of key enzymes of phospholipid and sphingolipid metabolism
Author(s) -
Mandal Asim K.,
Zhang Zhongjian,
Chou Janice Y.,
Mukherjee Anil B.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0831fje
Subject(s) - sphingomyelin , sphingolipid , microbiology and biotechnology , kinase , chemistry , ceramide , biochemistry , biology , membrane , apoptosis
Although the pancreatic secretory phospholipase A 2 (sPLA 2 IB) is considered a digestive enzyme, it has several important, nonenzymatic, receptor‐mediated functions. In this study, we demonstrate that via its receptor, sPLA 2 IB stimulates the expression of cytosolic PLA 2 (cPLA 2 )‐, cyclooxygenase‐2 (COX‐2)‐, Mg ++ ‐dependent neutral sphingomyelinase (NSMase)‐ and acid ceramidase (AC)‐mRNAs in NIH 3T3 cells. Moreover, through its receptor, sPLA 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 1β (IL‐1β), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) under identical conditions. These effects are not dependent on the catalytic activity of sPLA2IB, as both heat‐ and chemically inactivated enzyme induced these effects. Although protein kinase C and p38 mitogen‐activated protein kinases are critical for the sPLA 2 receptor‐mediated stimulation of expression of cytosolic PLA2 and cyclooxygenase‐2 mRNAs, respectively, the activation of these kinases is not required for neutral sphingomyelinase and acid ceramidase mRNA expression. Our results, for the first time, raise the possibility that, via its receptor, sPLA 2 IB plays important roles in the regulation of both phospholipid and sphingolipid metabolism.