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Glycogen synthase kinase‐3β negatively regulates group IIA phospholipase A 2 expression in human aortic smooth muscle and HepG2 hepatoma cells
Author(s) -
Menschikowski Mario,
Hagelgans Albert,
Hempel Ute,
Siegert Gabriele
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.09.067
Subject(s) - gsk 3 , glycogen synthase , kinase , chemistry , protein kinase c , phospholipase c , downregulation and upregulation , phospholipase , biochemistry , phospholipase a2 , enzyme , microbiology and biotechnology , biology , gene
The present study shows that the IFN‐γ‐mediated upregulation of secretory phospholipase A 2 of group IIA (sPLA 2 ‐IIA) in HASMC and HepG2 cells is synergistically increased after simultaneous inhibition of glycogen synthase kinase‐3β (GSK‐3β) by indirubin‐3 ′ ‐monoxime, 5‐iodo or AR‐A014418. The effect of GSK‐3β inhibition was dose‐ and time‐dependent and can be further augmented by its concomitant incubation with Clostridium difficile toxin B, an inhibitor of small Rho proteins, or H‐1152, an inhibitor of Rho‐associated kinase. Using AG‐490 and caffeic acid phenethyl ester (CAPE), it is further demonstrated that the effect of GSK‐3β inhibition on sPLA 2 ‐IIA expression depends on Janus kinase‐2 and NF‐κB‐signaling.