Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Activation of protein kinase C is required for silica-induced activation of the MAP kinase-AP-1 pathway.

Authors
Ding-M; Lu-Y; Bowman-L; Huang-C; Castranova-V
Source
Med Lav 2002 Oct; 93(Suppl):S41
NIOSHTIC No.
20027145
Abstract
Silica particles are considered to be fibrogenic agents and have been recently designated as carcinogenic, but the mechanisms for cancer initiation and progression are not well understood. By using an AP-1-luciferase reporter cell line, we demonstrated that activator protein-1 (AP-1) activation by crystalline silica is through mitogen-activated protein kinases (MAPK), i.e.,ERKs and p38 kinases. The present study investigates the role of protein kinase C (PKC) in silica-induced activation of the MAPK-AP-1 pathway. Treatment of JB6 cells with freshly fractured silica stimulated translocation of PKC*, PKC*, and PKC, from the cytosol to the membrane and activated Ap-1 activity. Rotterin (a selective inhibitor of PKC*), RO-32-0432 (a relative specific inhibitor for PKC), and calphostic C and bisindolylmaleimide I (general PKC inhibitors for all the subtypes), inhibited silica-stimulated AP-1 actication. These effects of PKC inhibitors were dose dependent. Dominate negative mutant transfectants of PKC markedly blocked AP-1 activation induced by silica. Western blot analysis using phosphor-specific antibodies indicates that PKC inhibitors or dominant negative mutant transfectants of PKC also blocked silica-induced phosphor ylation of ERKs and p38 kinase. Thses results demonstrate that PKC", PKC*, and PKC, mediate silica induced AP-1 activation through MAP kinase (ERKs and p38 kinases) pathways.
Keywords
Silicates; Silicosis; Silica-dusts; Pulmonary-disorders; Pulmonary-function; Pulmonary-system-disorders; Fibrogenicity; Respiratory-system-disorders; Respiratory-irritants; Cellular-reactions; Cell-damage
CODEN
MELAAD
CAS No.
14808-60-7; 7631-86-9
Publication Date
20021025
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2003
NTIS Accession No.
NTIS Price
ISSN
0025-7818
NIOSH Division
HELD
Source Name
La Medicina del Lavoro. 3rd International Symposium on Silica, Silicosis, Cancer and Other Diseases, S. Margherita Ligure, 21-25 October 2002
State
WV, NY, OH
TOP