Secretory phospholipase A(2) induces apoptosis via a mechanism involving ceramide generation.
Secretory phospholipase A(2) (sPLA(2)) plays important roles in cellular signaling and various biological events. In this study, we examined the biological effects and the potential signaling mechanism of purified sPLA(2) in MV1Lu cells. Three types of snake venom sPLA(2) were purified and their enzymatic activities were characterized by using various lipid substrates prepared from [3H]-myristate-labeled cells and by determining their effects on the induction of arachidonic acid (AA) release. The purified sPLA(2) induced apoptosis in Mv1Lu cells in a dose- and time-dependent manner, and was associated with a rapid increase in the intracellular ceramide level. Similar apoptotic effects were observed in Mv1Lu cells treated with exogenous ceramide analog, C(2)- and C(8)-ceramide. Moreover, treatment of cells with sphingomyelinase (SMase), which reduced the intracellular SM level, enhanced the apoptotic response to sPLA(2)s. sPLA(2)s also displayed an inhibitory effect on bradykinin-induced phospholipase D (PLD) activity, which can be imitated by exogenous ceramide. Our data indicate that sPLA(2) induces cell apoptosis via a mechanism involving increased ceramide generation.
Zhao
Sheng
S
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Box 25, 320 Yue-Yang Road, Shanghai 200031, People's Republic of China.
Du
Xiao-Yan
XY
Chai
Min-Qiang
MQ
Chen
Jun-Song
JS
Zhou
Yuan-Chong
YC
Song
Jian-Guo
JG
D017836:Agkistrodon; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D005434:Flow Cytometry; D054501:Group II Phospholipases A2; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D019814:Myristic Acid / Q000378:metabolism; D010741:Phospholipases A / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction; D012910:Snake Venoms / Q000201:enzymology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
D002518:Ceramides; D007527:Isoenzymes; D010743:Phospholipids; D012910:Snake Venoms; D019814:Myristic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D013108:Sphingomyelin Phosphodiesterase