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Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway.

Authors
Ding-M; Huang-C; Lu-YJ; Bowman-L; Castranova-V; Vallyathan-V
Source
Am J Physiol, Lung Cell Mol Physiol 2006 Feb; 290(2):L291-L297
NIOSHTIC No.
20029338
Abstract
Crystalline silica has long been well established as a fibrogenic agent, and recent evidence has implicated it as a potential human carcinogen. However, the mechanisms of silica-induced disease development and progression are not well understood. Our previous studies demonstrated that crystalline silica is able to activate activator protein-1 (AP-1) through mitogen-activated protein kinase (MAPK) pathways. The present study investigates the possible involvement of protein kinase C (PKC) in silica-induced activation of the MAPK/AP-1 signal transduction pathway. Treatment of mouse epidermal cells (JB6 cell line) with freshly fractured silica stimulated translocation of PKCalpha and PKCepsilon from the cytosol to the membrane and activated AP-1 transcription activity. Pretreatment of cells with PKC inhibitors, including RO-32-0432, calphostin C, and bisindolylmaleimide I, inhibited silica-induced AP-1 activation and phosphorylation of ERKs and p38 kinase. These inhibitory effects by PKC inhibitors were dose dependent. Furthermore, overexpression of dominant negative mutant (DNM) of PKCalpha or PKCepsilon markedly blocked AP-1 activation as well as phosphorylation of ERKs and p38 kinase induced by freshly fractured silica. These results demonstrate that PKCalpha and PKCepsilon are essential in silica-induced AP-1 activation through the MAP kinase (ERKs and p38 kinases) pathway.
Keywords
Silica-dusts; Silicates; Fibrogenicity; Fibrogenesis; Carcinogens; Carcinogenicity; Carcinogenesis; Laboratory-animals; Animals; Animal-studies; Quartz-dust
Contact
M. Ding, PPRB, NIOSH, 1095 Willowdale Rd., Morgantown, WV 26505
CODEN
APLPE7
CAS No.
14808-60-7
Publication Date
20060201
Document Type
Journal Article
Email Address
mid5@cdc.gov
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1040-0605
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
WV; NY
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