Exposure of B-lineage Lymphoid Cells to Low Energy Electromagnetic Fields Stimulates Lyn Kinase

Abstract

Here, we present evidence that exposure of B-lineage lymphoid cells to low energy electromagnetic fields (EMF) stimulates the protein tyrosine kinases Lyn and Syk, results in tyrosine phosphorylation of multiple electrophoretically distinct substrates, and leads to downstream activation of protein kinase C (PKC). EMF exposure enhances protein tyrosine phosphorylation in Syk deficient but not in Lyn-deficient B-lineage lymphoid cells and stimulates Lyn kinase activity in wild-type as well as Syk-deficient B-lineage lymphoid cells. These results indicate that activation of Lyn kinase is sufficient and mandatory for EMF-induced tyrosine phosphorylation in B-lineage lymphoid cells. The PKC activity increases later than the Lyn activity and pretreatment with the PTK inhibitors genistein or herbimycin A abrogates the EMF-induced PKC signal. Thus, stimulation of Lyn is a proximal and mandatory step in EMF-induced activation of PKC in B-lineage lymphoid cells. Our observations prompt the hypothesis that a delicate growth regulatory balance might be altered in B-lineage lymphoid cells by EMF-induced activation of Lyn.

Viability of unstimulated lymphocytes exposed to extremely low frequency electromagnetic fields is dependent on intensity

“…The present hypothesis is further supported by a recent study on human keratinocytes subjected to UV irradiation, which resulted in the inhibition of caspase 9 by PI3K/Akt pathway [56]. Similarly, exposure of Blineage lymphoid cells to ELF-EMF stimulated the protein tyrosine kinases (Lyn kinase), that plays pivotal and myriad roles in initiation of signal cascades that affect proliferation and survival of B-lineage lymphoid cells [57]. A possible mechanism of inhibition of apoptosis by repression of caspase 9 in primary lymphocytes exposed to 100 µT (50 Hz) ELF-EMF is given in Figure 6.…”

Bruton's Tyrosine Kinase Activity and Inositol 1,4,5-Trisphosphate Production Are Not Altered in DT40 Lymphoma B Cells Exposed to Power Line Frequency Magnetic Fields

“…Further, in DT40 cells, BTK activity was shown to be required for EMF responsiveness (2). The results presented in these three publications provided multiple levels of evidence that support and strengthen the plausibility of the hypothesis that a delicate growth regulatory balance in Blineage lymphoid cells might be altered by EMF exposure (1,2,5). These findings are significant because they show that exposure of DT40 cells to a magnetic field with an intensity of 1 gauss affects a well understood signal transduction pathway involved in signaling through the B cell receptor (BCR).…”

“…Exposure of human B-lineage leukemia cells to a 1-gauss 60-Hz EMF resulted in an enhanced tyrosine phosphorylation profile of substrate proteins and in LYN and SYK proteintyrosine kinase (PTK) activation, followed by protein kinase C stimulation (5). The activation of protein kinase C was dependent on the activation of LYN kinase, a PTK of the Src family that is known to be involved in signal cascades affecting proliferation and survival of B-lymphoid cells.…”

“…DT40 cells, stimulated with 25 M pervanadate for 15 and 30 min in parallel with the sham-or EMF-exposed samples, showed a marked increase in tyrosine phosphorylation of a large number of substrate proteins. Uckun et al (5) showed that protein tyrosine phosphorylation of substrate proteins was maximally stimulated in DT40 cells exposed for 1 min to a 1-gauss 60-Hz EMF. However, we found no detectable effect on protein tyrosine phos- (19).…”

Stimulation of Src Family Protein-tyrosine Kinases as a Proximal and Mandatory Step for SYK Kinase-dependent Phospholipase Cγ2 Activation in Lymphoma B Cells Exposed to Low Energy Electromagnetic Fields

“…In a recent study, we discovered that exposure of B-lineage lymphoid cells to low energy EMF stimulates LYN as well as its downstream substrate SYK (18). These results prompted the hypothesis that a delicate growth regulatory balance might be altered in B-lineage lymphoid cells by EMF-induced activation of a biochemical signaling cascade intimately linked to LYN kinase.…”