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

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

International Standard Serial Number (ISSN)

  • 0741-5400

Language

  • eng

Conference Location

  • United States