title: Activation of mitogen-activated protein kinases by tributyltin in CCRF-CEM cells: role of intracellular Ca(2+).
abstract: Effects of tributyltin chloride (TBT) and other organotin compounds on mitogen-activated protein kinases (MAPKs) were examined in CCRF-CEM human T lymphoblastoid cells. In response to the incubation with 0.25-2 microM TBT for 1 h, the levels of the phosphorylated form of extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK increased in a dose-dependent manner. The phosphorylation was observed after 15 min and lasted for 4 h following exposure to 1 microM TBT, while the cell viability was not lowered significantly within 6 h. On the other hand, no clear changes were found in the total protein levels of ERK, JNK, and p38 MAPK. The in vitro activities of MAPKs also increased in response to TBT exposure. The potentials of MAPKs phosphorylation and of cellular damage were TBT > dibutyltin dichloride (DBT) > monobutyltin trichloride (MBT). When compared to other triorganotin compounds such as trimethyltin chloride (TMT), triphenyltin chloride (TPT), and triethyltin bromide (TET), TBT exposure induced the most marked phosphorylation of MAPKs. Chelation of intracellular Ca(2+) suppressed TBT-induced MAPKs phosphorylation almost completely, but removal of external Ca(2+) did not. The present results showed that tributyltin is a potent activator of ERK, JNK, and p38 MAPK pathways, and Ca(2+) mobilized from intracellular stores plays an important role for the phosphorylation of MAPKs in this human T cell line.
authors.affiliation: Department of Environmental Toxicology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Matsuoka
authors.forename: B
authors.initials: B
authors.lastname: Wispriyono
authors.forename: Y
authors.initials: Y
authors.lastname: Iryo
authors.forename: H
authors.initials: H
authors.lastname: Igisu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology*; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D009947:Organotin Compounds / Q000633:toxicity; D014220:Trialkyltin Compounds / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002614:Chelating Agents; D009947:Organotin Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin; D004533:Egtazic Acid; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium