title: Activation of in situ tissue transglutaminase by intracellular reactive oxygen species.
abstract: We have investigated the novel function of intracellular reactive oxygen species (ROS) in the activation of in situ tissue transglutaminase (tTGase) by lysophosphatidic acid (LPA) and transforming growth factor-beta (TGF-beta) in Swiss 3T3 fibroblasts. LPA induced a transient increase of intracellular ROS with a maximal increase at 10 min, which was blocked by ROS scavengers, N-acetyl-L-cysteine and catalase. LPA activated tTGase with a maximal increase at 1h, which was inhibited by cystamine and ROS scavengers. Incubation with exogenous H(2)O(2) activated tTGase. TGF-beta also activated tTGase with a maximal activation at 2h and the tTGase activation was inhibited by the ROS scavengers. Scrape-loading of C3 transferase inhibited the ROS production and in situ tTGase activation by LPA and TGF-beta, and the inhibitory effect of C3 transferase was reversed by exogenous H(2)O(2). Microinjection of GTPgammaS inhibited transamidating activity of tTGase stimulated by LPA, TGF-beta, and maitotoxin. These results suggested that intracellular ROS was essential for the activation of in situ tTGase in response to LPA and TGF-beta.
authors.affiliation: Cell Research Team, Korea Basic Science Institute, Taejon 305-333, Republic of Korea.
authors.forename: Zee-Won
authors.initials: ZW
authors.lastname: Lee
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kwon
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Kim
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Yi
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000008:administration & dosage / Q000494:pharmacology; D007700:Kinetics; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008845:Microinjections; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins