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Beryllium fluoride‐induced cell proliferation: a process requiring P21 ras ‐dependent activated signal transduction and NF‐κB‐dependent gene regulation
Author(s) -
Misra Uma Kant,
Gawdi Govind,
Pizzo Salvatore Vincent
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.3.487
Subject(s) - signal transduction , creb , biology , mapk/erk pathway , microbiology and biotechnology , intracellular , inositol , phosphorylation , kinase , cell growth , transcription factor , endocrinology , medicine , biochemistry , gene , receptor
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‐κB 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.