Activation of mitogen-activated protein kinases by tributyltin in CCRF-CEM cells: Role of intracellular Ca2+

Zheng Ping Yu, Masato Matsuoka, Bambang Wispriyono, Yoshihisa Iryo, Hideki Igisu

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52 Citations (Scopus)


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 μM TBT for 1 h, the levels of the phosphorylated form of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-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 μM 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 Ca2+ suppressed TBT-induced MAPKs phosphorylation almost completely, but removal of external Ca2+ did not. The present results showed that tributyltin is a potent activator of ERK, JNK, and p38 MAPK pathways, and Ca2+ mobilized from intracellular stores plays an important role for the phosphorylation of MAPKs in this human T cell line. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalToxicology and Applied Pharmacology
Issue number3
Publication statusPublished - 1 Nov 2000


  • CCRF-CEM cells
  • ERK
  • Intracellular Ca
  • JNK
  • Organotin compounds
  • Tributyltin
  • p38 MAPK


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