Beryllium fluoride-induced cell proliferation: a process requiring P21(ras)-dependent activated signal transduction and NF-kappaB-dependent gene regulation.

Published

Journal Article

We studied the effect of beryllium fluoride on murine peritoneal macrophages and determined its effects on signal transduction and genetic regulation. At low concentration (1-5 nM), BeF(2) caused an approximate twofold increase in [(3)H]thymidine uptake and cell number, but above 5 nM, it showed cytotoxic effects. BeF(2) increased cellular inositol (1,4,5)trisphosphate (IP(3)) and [Ca(2)(+)](i) about twofold. The rise in [Ca(2)(+)](i) occurred consequent to release from IP(3)-sensitive Ca(2)(+) stores and from influx, mainly via L-type channels. A significant increase in the levels of MEK1, ERK1, p38 MAPK, and JNK phosphorylation was observed in BeF(2)-exposed macrophages. The levels of NF-kappaB and CREB transcription factors and the proto-oncogenes c-fos and c-myc were also elevated significantly. Intracellular Ca(2)(+) chelation blocked the effect of BeF(2). We conclude that BeF(2) at low concentration exerts its mitogenic effects in peritoneal macrophages by elevating [Ca(2)(+)](i), which triggers the activation of p21(ras)-dependent MAPK signaling cascades.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Gawdi, G; Pizzo, SV

Published Date

  • March 2002

Published In

Volume / Issue

  • 71 / 3

Start / End Page

  • 487 - 494

PubMed ID

  • 11867686

Pubmed Central ID

  • 11867686

International Standard Serial Number (ISSN)

  • 0741-5400

Language

  • eng

Conference Location

  • United States