Group VIB Ca2+-independent phospholipase A2γ promotes cellular membrane hydrolysis and prostaglandin production in a manner distinct from other intracellular phospholipases A2

Makoto Murakami, Seiko Masuda, Kaori Ueda-Semmyo, Emiko Yoda, Hiroshi Kuwata, Yasukazu Takanezawa, Junken Aoki, Hiroyuki Arai, Hideki Sumimoto, Yukio Ishikawa, Toshiharu Ishii, Yoshihito Nakatani, Ichiro Kudo

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Abstract

Although group VIA Ca2+-independent phospholipase A 2β (iPLA2β) has been implicated in various cellular events, the functions of other iPLA2 isozymes remain largely elusive. In this study, we examined the cellular functions of group VIB IPLA2γ. Lentiviral transfection of IPLA2γ into HEK293 cells resulted in marked increases in spontaneous, stimulus-coupled, and cell death-associated release of arachidonic acid (AA), which was converted to prostaglandin E2 with preferred cyclooxygenase (COX)-1 coupling. Conversely, treatment of HEK293 cells with iPLA2γ small interfering RNA significantly reduced AA release, indicating the participation of endogenous IPLA2γ. iPLA2γ protein appeared in multiple sizes according to cell types, and a 63-kDa form was localized mainly in peroxisomes. Electrospray ionization mass spectrometry of cellular phospholipids revealed that iPLA2γ and other intracellular PLA2 enzymes acted on different phospholipid subclasses. Transfection of iPLA2γ into HCA-7 cells also led to increased AA release and prostaglandin E2 synthesis via both COX-1 and COX-2, with a concomitant increase in cell growth. Immunohistochemistry of human colorectal cancer tissues showed elevated expression of iPLA2γ in adenocarcinoma cells. These results collectively suggest distinct roles for iPLA2β and iPLA2γ in cellular homeostasis and signaling, a functional link between peroxisomal AA release and eicosanoid generation, and a potential contribution of iPLA2γ to tumorigenesis.

Original languageEnglish
Pages (from-to)14028-14041
Number of pages14
JournalJournal of Biological Chemistry
Volume280
Issue number14
DOIs
Publication statusPublished - 2005 Apr 8
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Murakami, M., Masuda, S., Ueda-Semmyo, K., Yoda, E., Kuwata, H., Takanezawa, Y., Aoki, J., Arai, H., Sumimoto, H., Ishikawa, Y., Ishii, T., Nakatani, Y., & Kudo, I. (2005). Group VIB Ca2+-independent phospholipase A2γ promotes cellular membrane hydrolysis and prostaglandin production in a manner distinct from other intracellular phospholipases A2. Journal of Biological Chemistry, 280(14), 14028-14041. https://doi.org/10.1074/jbc.M413766200