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Acrylonitrile‐induced extracellular signal‐regulated kinase (ERK) activation via protein kinase C (PKC) in SK‐N‐SH neuroblastoma cells
Author(s) -
Chantara Wantika,
Watcharasit Piyajit,
Thiantanawat Apinya,
Satayavivad Jutamaad
Publication year - 2006
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1171
Subject(s) - protein kinase c , mapk/erk pathway , extracellular signal regulated kinases , kinase , cyclin dependent kinase 9 , ask1 , mitogen activated protein kinase kinase , extracellular , map kinase kinase kinase , chemistry , mitogen activated protein kinase 3 , microbiology and biotechnology , signal transduction , protein kinase a , cancer research , map2k7 , neuroblastoma , cyclin dependent kinase 2 , biology , cell culture , genetics
Acrylonitrile (ACN) is classified by IARC as a probable carcinogen. Chronic exposure to ACN increases the incidence of tumors in various organs of test animals, including the brain and lung. ERK1/2 activation plays crucial roles in cell proliferation and is involved in many steps of tumor progression. Therefore, this study examined whether ACN altered the activation state of ERK1/2 in human neuroblastoma SK‐N‐SH cells. Treatment of these cells with ACN greatly increased phosphorylation of ERK1/2 in dose‐ and time‐dependent manners. This effect was inhibited by PD 98059 and U 0126, specific inhibitors of MEK, indicating that MEK, an upstream activator of ERK1/2, was directly involved in ACN‐induced ERK1/2 activation. Furthermore, the activation of ERK1/2 by ACN was attenuated by inhibition of PKC with GF 109203X, rottlerin and prolonged incubation with PMA (phorbol 12‐myristate 13‐acetate). This demonstrated the participation of PKC in the ACN‐stimulated activation of ERK1/2. Taken together, our results indicate that ACN‐induced ERK1/2 activation involves PKC through a MEK‐dependent pathway. Copyright © 2006 John Wiley & Sons, Ltd.