tailieunhanh - Báo cáo Y học: Group IID heparin-binding secretory phospholipase A2 is expressed in human colon carcinoma cells and human mast cells and up-regulated in mouse inflammatory tissues

Group IID secretory phospholipase A2 (sPLA2-IID), a heparin-binding sPLA2 that is closely related to sPLA2-IIA, augments stimulus-induced cellular arachidonate release in a manner similar to sPLA2-IIA. Here we identified the residues of sPLA2-IID that are responsible for heparanoid binding, are and therefore essential for cellular function. Mutating four cationic residues in the C-terminal portion of sPLA2-IID resulted in abolition of its ability to associate with cell surface heparan sulfate and to enhance stimulusinduced delayed arachidonate release, cyclooxygenase-2 induction, and prostaglandin generation in 293 cell transfectants | Eur. J. Biochem. 269 2698-2707 2002 FEBS 2002 doi Group IID heparin-binding secretory phospholipase A2 is expressed in human colon carcinoma cells and human mast cells and up-regulated in mouse inflammatory tissues Makoto Murakami1 Kumiko Yoshihara1 Satoko Shimbara1. Masatsuau Sawada2 Naoki Inaaaki2 Hiroichi Nagai2 Mikihiko Naito3 Takashi Tsuruo3 Tae Churl Moon4 Hyeun Wook Chang4 and Ichiro Kudo1 1Department of Health Chemistry School of Pharmaceutical Sciences Showa University Tokyo 2Pharmacological Department Gifu College of Pharmacy Gifu Japan 3Institute of Molecular and Cellular Biosciences University of Tokyo Tokyo Japan 4College of Pharmacy Yeungnam University Gyonsan Korea Group IID secretory phospholipase A2 sPLA2-IID a heparin-binding sPLA2 that is closely related to sPLA2-IIA augments stimulus-induced cellular arachidonate release in a manner similar to sPLA2-IIA. Here we identified the residues of sPLA2-IID that are responsible for heparanoid binding are and therefore essential for cellular function. Mutating four cationic residues in the C-terminal portion of sPLA2-IID resulted in abolition of its ability to associate with cell surface heparan sulfate and to enhance stimulus-induced delayed arachidonate release cyclooxygenase-2 induction and prostaglandin generation in 293 cell trans-fectants. As compared with several other group II subfamily sPLA2s which were equally active on A23187- and IL-1-primed cellular membranes sPLA2-IID showed apparent preference for A23187-primed membranes. Several human colon carcinoma cell lines expressed sPLA2-IID and sPLA2-X constitutively the former of which was negatively regulated by IL-1. sPLA2-IID but not other sPLA2 isozymes was expressed in human cord blood-derived mast cells. The expression of sPLA2-IID was significantly altered in several tissues of mice with experimental inflammation. These results indicate that sPLA2-IID may be involved in inflammation in cell- and .