Glycogen synthase kinase-3beta negatively regulates group IIA phospholipase A2 expression in human aortic smooth muscle and HepG2 hepatoma cells.
The present study shows that the IFN-gamma-mediated upregulation of secretory phospholipase A2 of group IIA (sPLA2-IIA) in HASMC and HepG2 cells is synergistically increased after simultaneous inhibition of glycogen synthase kinase-3beta (GSK-3beta) by indirubin-3'-monoxime, 5-iodo or AR-A014418. The effect of GSK-3beta 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-3beta inhibition on sPLA2-IIA expression depends on Janus kinase-2 and NF-kappaB-signaling.
Menschikowski
Mario
M
Medizinische Fakultät Carl Gustav Carus, Institut für Klinische Chemie und Laboratoriumsmedizin, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. menschik@rcs1.urz.tu-dresden.de
Hagelgans
Albert
A
Hempel
Ute
U
Siegert
Gabriele
G
D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017931:DNA Primers; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D053614:Janus Kinase 2; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
D017931:DNA Primers; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D010741:Phospholipases A; D054467:Phospholipases A2