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Induction of activator protein-1 through reactive oxygen species by crystalline silica in JB6 cells.

Authors
Ding-M; Shi-X; Lu-Y; Huang-C; Leonard-S; Roberts-J; Antonini-J; Castranova-V; Vallyathan-V
Source
J Biol Chem 2001 Mar; 276(12):9108-9114
NIOSHTIC No.
20021716
Abstract
We reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. We found that FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and oxygen consumption support the conclusion that ROS are generated by silica-treated cells. N-Acetylcysteine (an antioxidant) and polyvinyl pyridine-N-oxide (an agent that binds to Si-OH groups on silica surfaces) decreased AP-1 activation and phosphorylation of ERKs and p38 kinase. Catalase inhibited phosphorylation of ERKs and p38 kinase, as well as AP-1 activation induced by FFSi, suggesting the involvement of H(2)O(2) in the mechanism of silica-induced AP-1 activation. Sodium formate (an ( small middle dot)OH scavenger) had no influence on silica-induced MAPKs or AP-1 activation. Superoxide dismutase enhanced both AP-1 and MAPKs activation, indicating that H(2)O(2), but not O(2), may play a critical role in silica-induced AP-1 activation. These studies indicate that freshly ground silica is more biologically active than aged silica and that ROS, in particular H(2)O(2), play a significant role in silica-induced AP-1 activation.
Keywords
Exposure-levels; Silicosis; Cancer; Lung-cancer; Animal-studies; Laboratory-animals; Silicates; Silica-dusts
Contact
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
JBCHA3
CAS No.
14808-60-7
Publication Date
20010323
Document Type
Journal Article
Email Address
vav1@cdc.gov
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
12
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV
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