Activation of c-jun N-terminal kinase in A549 lung carcinoma cells by sodium dichorate: Role of dissociation of apoptosis signal regulating kinase-1 from 1β physiological inhibitor thioredoxin

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Colleges, School and Institutes

Abstract

Changes in the components of the Jun N-terminal kinase (JNK) signalling pathway were investigated in human A549 lung carcinoma cells treated with sodium dichromate. Sodium dichromate (100 muM, 0-6 h) failed to activate nuclear factor kappa B (NF-kappaB) as determined by a lack of nuclear translocation of p65 but resulted in Jun N-terminal kinase activation as assessed by phospho-Jun N-terminal kinase Western blotting in a dose-dependent (>25 muM) and time-dependent (>1 h) manner. In addition, c-Jun, a downstream target of Jun N-terminal kinase signalling was also activated with a similar dose- and time-dependency at the level of both protein expression and degree of phosphorylation. In contrast, sodium dichromate treatment had no effect on levels of phospho-p38. Immunoprecipitation demonstrated that apoptosis signal regulating kinase-1 (ASK-1), an upstream activator of Jun N-terminal kinase was dissociated from its inhibitory partner thioredoxin (Trx) in response to sodium dichromate (100 muM, 4 h) treatment. This treatment was also associated with a transient (2 h) increase in cytosolic levels of thioredoxin but no nuclear translocation of thioredoxin was observed. In conclusion, sodium dichromate had a stimulatory effect on the Jun N-terminal kinase signalling pathway in A549 cells, resulting in activation of downstream effector molecules. We hypothesise that dissociation of apoptosis signal regulating kinase-1 from thioredoxin may be at least partially responsible for Jun N-terminal kinase activation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Details

Original languageEnglish
Pages (from-to)101-112
Number of pages12
JournalToxicology
Volume197
Publication statusPublished - 1 Jan 2004

Keywords

  • sodium dichromate, Jun N-terminal kinase, A549 lung carcinoma cells