Involvement of the extracellular signal-regulated protein kinase (ERK) pathway in the induction of apoptosis by cadmium chloride in CCRF-CEM cells

Yoshihisa Iryo, Masato Matsuoka, Bambang Wispriyono, Tsutomu Sugiura, Hideki Igisu

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

When CCRF-CEM cells were incubated with 5-40 μM CdCl2, apoptosis was observed most clearly at 10 μM. Prior to the development of apoptosis, mitogen-activated protein kinases (MAPKs), i.e. extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, were activated with different sensitivity to CdCl2 exposure. ERK and p38 MAPK were phosphorylated with incubation of 1 μM CdCl2, but higher than 20 μM CdCl2 was required for the clear phosphorylation of JNK. In the time-course study, ERK and p38 MAPK were phosphorylated earlier than JNK after CdCl2 exposure. The in vitro activities of MAPKs also increased in response to CdCl2 exposure. Pretreatment with an intracellular Ca2+ chelator, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM), suppressed almost completely CdCl2-induced phosphorylation of JNK and p38 MAPK, but not ERK phosphorylation, indicating that the activation of JNK and p38 MAPK depends on the intracellular Ca2+ but that of ERK does not. On the other hand, treatment with a MAPK/ERK kinase (MEK) inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), suppressed CdCl2-induced ERK activation and the apoptosis as well. The inhibition of p38 MAPK activity with SB203580 (4-[4-fluorophenyl]-2-[4-methylsulfinylphenyl]-5-[4-pyridyl]1H-im idazole) did not protect cells from apoptosis. The present results showed that the activation of ERK, JNK, and p38 MAPK is differently regulated in CCRF-CEM cells exposed to CdCl2, and that the ERK pathway seems to be responsible for the induction of apoptosis by CdCl2 exposure in this human T cell line. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1875-1882
Number of pages8
JournalBiochemical Pharmacology
Volume60
Issue number12
DOIs
Publication statusPublished - 15 Dec 2000

Keywords

  • Apoptosis
  • CCRF-CEM cells
  • Cadmium
  • ERK
  • JNK
  • P38 MAPK

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