Different functional aspects of the group II subfamily (types IIA and V) and type X secretory phospholipase A2s in regulating arachidonic acid release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation

Makoto Murakami, Terumi Kambe, Satoko Shimbara, Ken Ichi Higashino, Kohji Hanasaki, Hitoshi Arita, Masakuni Horiguchi, Makoto Arita, Hiroyuki Arai, Keizo Inoue, Ichiro Kudo

研究成果: Article

155 引用 (Scopus)


We have recently reported that members of the heparin-binding group II subfamily of secretory PLA2s (sPLA2s) (types IIA and V), when transfected into 293 cells, released [3H]arachidonic acid (AA) preferentially in response to interleukin-1 (IL-1) and acted as 'signaling' PLA2s that were functionally coupled with prostaglandin biosynthesis. Here we show that these group II subfamily sPLA2s and the type X sPLA2 behave in a different manner, the former being more efficiently coupled with the prostaglandin- biosynthetic pathway than the latter, in 293 transfectants. Type X sPLA2, which bound only minimally to cell surface proteoglycans, augmented the release of both [3H]AA and [3H]oleic acid in the presence of serum but not IL-1. Both types IIA and V sPLA2, the AA released by which was efficiently converted to prostaglandin E2, markedly augmented IL-1-induced expression of cyclooxygenase (COX)-2 in a heparin-sensitive fashion, whereas type X sPLA2 lacked the ability to augment COX-2 expression, thereby exhibiting the poor prostaglandin E2-biosynthetic response unless either of the COX isozymes was forcibly introduced into type X sPLA2-expressing cells. Implication of phospholipid scramblase, an enzyme responsible for the perturbation of plasma membrane asymmetry, revealed that the scramblase-transfected cells became more sensitive to types IIA and V, but not X, sPLA2, releasing both [3H]AA and [3]oleic acid in an IL-1-independent manner. Thus, although phospholipid scramblase-mediated alteration in plasma membrane asymmetry actually led to the increased cellular susceptibility to the group II subfamily of sPLA2s, several lines of evidence suggest that it does not entirely mimic their actions on cells after IL-1 signaling. Interestingly, coexpression of type IIA or V, but not X, sPLA2 and phospholipid scramblase resulted in a marked reduction in cell growth, revealing an unexplored antiproliferative aspect of particular classes of sPLA2.

ジャーナルJournal of Biological Chemistry
出版物ステータスPublished - 1999 10 29


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology