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Silica induces cell cycle changes through PI-3K/AP-1 pathway in human embryo lung fibroblast cells.
Jia-XW; Liu-BC; Ye-M; Liu-HF; Shi-XL
Cell Biochem Funct 2010 Oct; 28(7):613-619
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.
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
Bingci Liu, National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nan Wei Road, Beijing, China 100050
Issue of Publication
Cell Biochemistry & Function
Page last reviewed: May 5, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division