TY - JOUR
T1 - 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
AU - Hodges, Nikolas
AU - Smart, Oliver
AU - Lee, Amanda
AU - Lewis, Nicholas
AU - Chipman, James
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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.
AB - 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.
KW - sodium dichromate
KW - Jun N-terminal kinase
KW - A549 lung carcinoma cells
UR - http://www.scopus.com/inward/record.url?scp=1442348218&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2003.12.004
DO - 10.1016/j.tox.2003.12.004
M3 - Article
C2 - 15003321
VL - 197
SP - 101
EP - 112
JO - Toxicology
JF - Toxicology
ER -