Roles of the ERK, JNK/AP-1/cyclin D1-CDK4 pathway in silica-induced cell cycle changes in human embryo lung fibroblast cells

Details

• Personal Author:
  Jia X ; Liu B ; Liu H ; Shi X ; Ye M ; Zhang F
• Description:
  Silica is a potent occupational fibrogenic agent capable of inducing lung fibrosis and many other lung diseases. Our current study focused on the signalling pathways regulating cell cycle changes in HELF (human embryo lung fibroblast) after silica (alpha-quartz) exposure. Our results showed silica exposure could lead to cell cycle changes. The cell cycle alternations were accompanied with overexpression of cyclin D1 and CDK4 (cyclin-dependent kinase 4) in a time-dependent manner. Silica exposure also decreased E2F-4 expression in HELF. These changes were blocked by overexpression of dominant-negative mutants of ERK (extracellular signal-regulated protein kinase) or the JNK (stress-activated c-Jun NH(2)-terminal kinase), respectively. Moreover, pretreatment of cells with curcumin, an activation of AP-1 (activator protein-1) inhibitor, inhibited silica-induced cell cycle alteration, the decreased expression of E2F-4 and overexpression of cyclin D1 and CDK4. Furthermore, both antisense cyclin D1 and antisense CDK4 can block silica-induced cell cycle changes. These results suggest that silica exposure can induce cell cycle changes, which may be mediated through ERK, JNK/AP-1/cyclin D1-CDK4-dependent pathway. [Description provided by NIOSH]
• Subjects:
  Hazardous Substances Neoplasms Occupational Health Particulate Matter Safety Silicon Dioxide Workplace
• Keywords:
  Author Keywords: Cell Cycle Biohazards Biological-effects Biological-systems Cancer-rates Cell-function Cell-metabolism Cell-transformation Cellular-function Cellular-reactions Fibrogenicity Fibrous-bodies HELF Lung Fibrosis Occupational Particulate-dust Particulates Signalling Pathway Silica Work-areas Work-operations Worker-health

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• ISSN:
  1065-6995
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  35
• Issue:
  7
• NIOSHTIC Number:
  nn:20039628
• Citation:
  Cell Biol Int 2011 Jul; 35(7):697-704
• Email:
  bcliu@263.net
• CAS Registry Number:
  Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  True
• Source Full Name:
  Cell Biology International
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:20b9e4b3021de3b3903ef4179eca4dd5cedbbe734064e8920dbe9805c58a093c6e7d8ff4c9f61272890a726458dc88e7b9819f349c575e51107fba7cffc20507
• Download URL:
  https://stacks.cdc.gov/view/cdc/192801/cdc_192801_DS1.pdf
• File Type:
  [PDF - 179.84 KB ]