The inhibitory effect of acrylamide on NCAM expression in human neuroblastoma cells: involvement of CK2/Ikaros signaling pathway.
Acrylamide has been known to have a neurotoxic effect which is associated with nerve damage in both the central and peripheral nervous systems. Since neural cell adhesion molecule (NCAM) plays an important role in the processes of neuronal development and synaptic plasticity, the down-regulation of NCAM may lead impaired spatial memory and reduced long-term potentiation. We examined the effect of acrylamide on NCAM expression and the mechanisms of its effect in human neuroblastoma cells. Treatment with acrylamide resulted in the decrease of NCAM expression, which was reversed by CK2 inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB). Moreover, Western blot analysis showed that acrylamide induced the expression of CK2. Acrylamide dose-dependently decreased the DNA binding affinity of the Ikaros transcription factor, which is a bifunctional differentiation factor. In addition, the cells treated with acrylamide and CK2 inhibitor showed increased Ikaros activity compared with the acrylamide treatment only. Small interfering RNA-mediated depletion of CK2-α also increased Ikaros activity in acrylamide-treated cells. Overall, these data suggest that acrylamide decreases the Ikaros DNA binding activity via the CK2 pathway, resulting in a decrease of NCAM expression and provide further insight into the mechanisms underlying acrylamide actions.
Lee
Hye-Rim
HR
Division of Immunopharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
Cho
Seong-Jun
SJ
Park
Hye-Jin
HJ
Kim
Kyung-Ho
KH
Rhee
Dong-Kwon
DK
Pyo
Suhkneung
S
D020106:Acrylamide / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000187:drug effects* / Q000235:genetics; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D019006:Neural Cell Adhesion Molecules; D051740:Ikaros Transcription Factor; D020106:Acrylamide; D004247:DNA; D047390:Casein Kinase II