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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.

Authors
Kang-JL; Lee-HS; Pack-IS; Castranova-V
Source
FASEB J 2002 Mar; 16(5):A1161
NIOSHTIC No.
20023399
Abstract
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.
Keywords
Silica-dusts; Silicates; Antioxidants; Antioxidation; Cell-function
CODEN
FAJOEC
CAS No.
55520-40-6
Publication Date
20020322
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0892-6638
NIOSH Division
HELD
Source Name
The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002
State
WV; LA
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