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

Citation
M. Ding et al., Induction of activator protein-1 through reactive oxygen species by crystalline silica in JB6 cells, J BIOL CHEM, 276(12), 2001, pp. 9108-9114
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
12
Year of publication
2001
Pages
9108 - 9114
Database
ISI
SICI code
0021-9258(20010323)276:12<9108:IOAPTR>2.0.ZU;2-8
Abstract
We reported previously that freshly fractured silica (FFSi) induces activat or protein-1 (AP-1) activation through extracellular signal-regulated prote in kinases (ERKs) and p38 kinase pathways. In the present study, the biolog ic activities of FFSi and aged silica (ASi) were compared by measuring thei r 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 ac tivation mere also investigated. We found that FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused grea ter phosphorylation of ERKs and p38 kinase than ASi, FFSi generated more RO S than ASi when incubated with the cells as measured by electron spin reson ance (ESR). Studies using ROS-sensitive dyes and oxygen consumption support the conclusion that ROS are generated by silica-treated cells. N-Acetylcys teine (an antioxidant) and polyvinyl pyridine-N-oxide (an agent that binds to Si-OH groups on silica surfaces) decreased AP-1 activation and phosphory lation of ERKs and p38 kinase. Catalase inhibited phosphorylation of ERKs a nd p38 kinase, as well as AP-1 activation induced by FFSi, suggesting the i nvolvement of H2O2 in the mechanism of silica-induced AP-1 activation. Sodi um formate (an (OH)-O-. scavenger) had no influence on silica-induced MAPKs or AP-1 activation. Superoxide dismutase enhanced both AP-1 and MAPKs acti vation, indicating that H2O2, but not O-2(radical anion), may play a critic al role in silica-induced AP-I activation. These studies indicate that fres hly ground silica is more biologically active than aged silica and that ROS , in particular H2O2, play a significant role in silica-induced AP-I activa tion.