Stimulation of Bruton's tyrosine kinase (BTK) and inositol 1,4,5-trisphosphate production in leukemia and lymphoma cells exposed to low energy electromagnetic fields.
We examined the effects of low energy electromagnetic field (EMF) exposure on the BTK kinase activity in B18-2 ([Btk-, rBTK(wt)] DT40) chicken lymphoma B cells and NALM-6 leukemic pre-B cells. Exposure of B 18-2 cells to EMF resulted in activation of BTK within 1 to 15 minutes in 8 of 8 independent experiments with stimulation indexes ranging from 1.2 to 13.3. While in some experiments the BTK stimulation was transient, in others the BTK activity continued to be significantly elevated for up to 4 hours. Similarly, exposure of NALM-6 cells to EMF resulted in activation of BTK within 30 minutes in 7 of 7 experiments with stimulation indexes ranging from 1.2 to 7.4. Stimulation of BTK activity in EMF exposed cells was associated with enhanced phosphoinositide turnover and increased inositol-1,4,5-trisphosphate (IP3) production in 7 of 13 experiments with DT40 cells and 7 of 13 experiments with NALM-6 cells. The likelihood and magnitude of an IP3 response after EMF exposure were similar to those after BCR ligation on DT40 cells and CD19 ligation on NALM-6 cells. These results confirm and extend our previous studies regarding EMF-induced biochemical signaling events in B-lineage lymphoid cells.
Dibirdik
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I
Department of Biochemistry, Parker Hughes Institute, Roseville, Minnesota 55113, USA. idibirdik@mercury.ih.org
Bofenkamp
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M
Skeben
P
P
Uckun
F
F
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002645:Chickens; D004574:Electromagnetic Fields; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000528:radiation effects*; D007527:Isoenzymes / Q000378:metabolism / Q000528:radiation effects; D007700:Kinetics; D015448:Leukemia, B-Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D010738:Type C Phospholipases / Q000378:metabolism / Q000528:radiation effects
D007527:Isoenzymes; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D010738:Type C Phospholipases; D051966:Phospholipase C gamma