Phosphoinositide 3-Kinase Activity Leads to NF-kB Activation Through Interacting with Tyrosine-Phosphorylated IkB-A and Contributing to Tyrosine Phosphorylation of p65 NF-kB

Details

• Personal Author:
  Castranova, Vincent ; Kang JL ; Lee HS ; Pack IS
• Description:
  The role and mechanisms of PI3-kinase activity in NF-kB activation in silica-stimulated RAW 264.7 cells were investigated. Results indicate that the p85a subunit of PI3-kinase interacted with tyrosine-phosphorylated IkB-a in silica-stimulated cells. PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica-induced PI3-kinaseand NF-kB activation. The inhibition of NF-kB activation by PI3-kinase inhibitors was also observed in pervanadate-stimulated but not in LPS-stimulated cells. Furthermore, tyrosine phosphorylation of NF-kB p65 was enhanced in cells stimulated with silica, pervanadate, or LPS, and wortmannin substantially inhibited the phosphorylation event induced by these stimulants excluding LPS. Antioxidants, such as SOD, NAC and PDTC, blocked silica-induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-kB activation by mediating PI3-kinase activation. Our data suggest that p85 and p110 subnits of PI3-kinase play a role in NF-kB activation through interaction with IkB-a and contributing to tyrosine phosphorylation of p65 NF-kB. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Antioxidants Occupational Health Safety Silicon Dioxide
• Keywords:
  Antioxidation Cell Function Silica Dusts Silicates
• ISSN:
  0892-6638
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; 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:
  16
• Issue:
  5
• NIOSHTIC Number:
  nn:20023399
• Citation:
  FASEB J 2002 Mar; 16(5):A1161
• CAS Registry Number:
  L-Tyrosine (CAS RN 55520-40-6)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  False
• Source Full Name:
  The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e6074801973d9d30ea340e8e7cfca30c159be50f085ba9fcf559f19a60c07f30373622d0e37ae512084da42d2c8f7b946d962ae136384b162e49f9806ac76f69
• Download URL:
  https://stacks.cdc.gov/view/cdc/195849/cdc_195849_DS1.pdf
• File Type:
  [PDF - 501.50 KB ]