Ionizing radiation activates c-Jun NH2-terminal kinase (JNK/SAPK) via a PKC-dependent pathway in human thyroid cells.
Thyroid gland is known to be higher sensitive to carcinogenic effects of external ionizing radiation (IR) than other tissues. To clarify the cell-specific response following irradiation, activations of c-Jun NH2-terminal kinases (JNKs), which is one of mitogen-activated protein kinases (MAPKs) family members, and extracellular signal-regulated kinase (ERK) were examined in primary cultured human thyroid cells in comparison with human diploid fibroblast cells, WI-38. Although UV exposure strikingly induced JNK activity in both cells, the dose-response increase following IR exposure was observed in thyroid cells with the maximal JNK activity (3.5 fold induction) obtained at 10 Gy exposure, but no increase in WI-38 cells. The JNK activity was reached a maximum of 2.2 fold induction at 30 min after 5 Gy exposure and then sustained for at least 12 hr. On the other hand, ERK activity was not stimulated in thyroid cells following irradiation. The effects of 12-O-tetradecanoylphorbol beta-acetate (TPA) mimicked those of radiation on JNK cascade and 1-(5-isoquinolinesulphonyl)-2,5-dimethylpiperazine 2HCl (H7) and pretreatment with TPA blocked JNK activation following irradiation. Our results demonstrate that IR stimulates JNK activity in cultured human thyroid cells but not in fibroblasts indicating distinct activation and regulation mechanisms of JNK cascade. The JNK activation following IR exposure is mediated at least partially through a PKC-dependent pathway.
Hara
T
T
Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki, Japan.
Namba
H
H
Yang
T T
TT
Nagayama
Y
Y
Fukata
S
S
Kuma
K
K
Ishikawa
N
N
Ito
K
K
Yamashita
S
S
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism* / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases