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Silica induces cell cycle changes through PI-3K/AP-1 pathway in human embryo lung fibroblast cells.

Authors
Jia-XW; Liu-BC; Ye-M; Liu-HF; Shi-XL
Source
Cell Biochem Funct 2010 Oct; 28(7):613-619
NIOSHTIC No.
20037901
Abstract
Exposure to silica is associated with progressive pulmonary inflammation and fibrosis. Our previous study had demonstrated silica exposure could cause cell cycle alternation and activator protein-1 (AP-1) activation. This study showed that silica exposure induced phosphorylation of p70S6 kinase (p70S6K) and Akt in human embryo lung fibroblasts (HELFs). These changes were blocked by overexpression of dominant-negative mutants of phosphatidylinositol-3 kinase (Delta p85) or Akt (DN-Akt), respectively. Moreover, pretreatment of cells with rapamycin, a specific p70S6K inhibitor, could inhibit silica-induced cell cycle alteration, AP-1 activation, and phosphorylation of p70S6K, but had no effect on Akt phosphorylation. This suggested that phosphatidylinositol-3 kinase (PI-3K)/AP-1 pathway was likely responsible for cell cycle changes. Furthermore, we observed the effect of the pathway on cell cycle regulatory proteins. Our results indicated that inactivation of PI-3K, Akt, or p70S6K could inhibit silica-induced overexpression of cyclin DI and cyclin-dependent kinase 4 (CDK4) and decreased expression of E2F-4. Taken together, silica could induce cell cycle changes through PI-3K/AP-1 pathway in HELFs.
Keywords
Airway-resistance; Alveolar-cells; Cell-function; Cell-transformation; Cellular-function; Cellular-reactions; Cell-damage; Exposure-assessment; Exposure-levels; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Respiratory-irritants; Respiratory-system-disorders; Silicates; Silicon-compounds; Author Keywords: silica; cell cycle; signaling pathways; PI-3K
Contact
Bingci Liu, National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nan Wei Road, Beijing, China 100050
CODEN
CBFUDH
CAS No.
14808-60-7
Publication Date
20101012
Document Type
Journal Article
Email Address
bcliu@263.net
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
7
ISSN
0263-6484
NIOSH Division
HELD
Source Name
Cell Biochemistry & Function
State
WV
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