Involvement of p38 mitogen-activated protein kinase in the cell growth inhibition by sodium arsenite

Citation
Jy. Kim et al., Involvement of p38 mitogen-activated protein kinase in the cell growth inhibition by sodium arsenite, J CELL PHYS, 190(1), 2002, pp. 29-37
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELLULAR PHYSIOLOGY
ISSN journal
0021-9541 → ACNP
Volume
190
Issue
1
Year of publication
2002
Pages
29 - 37
Database
ISI
SICI code
0021-9541(200201)190:1<29:IOPMPK>2.0.ZU;2-0
Abstract
It is well-known that p38 mitogen-activated protein kinase (p38MAPK) partic ipates in cellular responses to mitogenic stimuli, environmental and genoto xic stresses, and apoptotic agents. Although there are several reports on p 38MAPK in relation to cell growth and apoptosis, the exact mechanism of p38 MAPK-mediated cell growth regulation remains obscure. Here, we examined pos sible roles of p38MAPK in the sodium arsenite-induced cell growth inhibitio n in NIH3T3 cells. Sodium arsenite induced transient cell growth delay with marked activation of p38MAPK. In addition, arsenite induced CDK inhibitor p21(CIP1/WAF1) and enhanced its binding to the CDK2, which resulted in inhi bition of CDK2 activity. The levels of cyclin D1 expression and the CDK4 ki nase activity were also significantly reduced. pRB was hypophosphorylated b y sodium arsenite. SB203580, a specific inhibitor of p38MAPK, blocked arsen ite-induced growth inhibition as well as the arsenite-induced p21(CIP1/WAF1 ) expression. Expression of dominant negative p38MAPK also blocked arsenite -induced p21(CIP1/WAF1) expression. Inhibited-CDK2 activity was also comple tely reversed by SB203580 or expression of dominant negative p38MAPK, while the decreased-cyclin D1 protein by the compound was not restored. These da ta demonstrate a possible link between the activation of p38MAPK and induct ion of p21(CIP1/WAF1), suggesting that the activation of p38MAPK is, at lea st in part, related to the cell growth inhibition by sodium arsenite. (C) 2 002 Wiley-Liss, Inc.