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Pulsed electrical fields cause activation of tyrosin kinase related cellular signalling in endothelial cells leading to transcription processes and angiogenesis
Author(s) -
Dissing Steen,
Tritsaris Katerina,
Hansen Anker Jon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1129.29
Subject(s) - angiogenesis , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , protein kinase b , kinase , mapk/erk pathway , signal transduction , phosphorylation , chemistry , tyrosine kinase , protein kinase a , biology , cancer research
We investigated if pulsed electrical fields cause enhanced endothelial cellular signalling and angiogenesis. Pulsed electrical fields were imposed on human and porcine endothelial cell cultures (HDMEC, PAE and HUVEC) by use of coils that create pulsed electromagnetic fields (PEMF) that create pulsed electrical fields of a magnitude of 1–10 mV/cm. PEMF activates cellular signalling related to tyrosin kinase receptor function since it evokes increased phosphorylation of MAPK signalling and Akt signalling pathways. The tyrosine kinase Src becomes phosphorylated at Tyr416 in the activation loop of the kinase domain, and dephosphorylated at Tyr527 located in the negative regulatory tail of the protein. Both mechanisms imply activation of the kinase. We propose that the Src enzyme is the sensor or is located close to the site that senses the changes in the electrochemical potential of protein charges. RT‐PCR analysis of brain derived neurotrophic factor (BDNF) mRNA revealed an upregulation after 3 h of PEMF exposure in HDMEC. In animal angiogenesis models we found an enhanced angiogenesis after 24 hours. Thus, PEMF induce endothelial cell activation and angiogenesis. We hypothesize that activation of brain endothelial cells (blood brain barrier) contributes to the beneficial effects by PEMF observed in a study of patients with depression (Martiny et al., Biol. Psychiatry, 68: 163–9, 2010).