Elf-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells

Objectives: Magnetic fields have been shown to affect cell proliferation an d growth factor expression in cultured cells, Although the activation of en dorphin systems is a recurring motif among the biological events elicited b y magnetic fields, compelling evidence indicating that magnetic fields may modulate opioid gene expression is still lacking. We therefore investigated whether extremely low frequency (ELF) pulsed magnetic fields (PMF) may aff ect opioid peptide gene expression and the signaling pathways controlling o pioid peptide gene transcription in the adult ventricular myocyte, a cell t ype behaving both as a target and as a source for opioid peptides. Methods: Prodynorphin gene expression was investigated in adult rat myocytes expose d to PMF by the aid of RNase protection and nuclear run-off transcription a ssays. In PMF-exposed nuclei, nuclear protein kinase C (PKC) activity was f ollowed by measuring the phosphorylation rate of the acrylodan-labeled MARC KS peptide. The effect of PMF on the subcellular distribution of different PKC isozymes was assessed by immunoblotting. A radioimmunoassay procedure c oupled to reversed-phase high performance liquid chromatography was used to monitor the expression of dynorphin B. Results: Here, we show that PMF enh anced myocardial opioid gene expression and that a direct exposure of isola ted myocyte nuclei to PMF markedly enhanced prodynorphin gene transcription , as in the intact cell. The PMF action was mediated by nuclear PKC activat ion but occurred independently from changes in PKC isozyme expression and e nzyme translocation. PMF also led to a marked increase in the synthesis and secretion of dynorphin B. Conclusions: The present findings demonstrate th at an opioid gene is activated by myocyte exposure to PMF and that the cell nucleus and nuclear embedded PKC are a crucial target for the PMF action. Due to the wide ranging importance of opioid peptides in myocardial cell ho meostasis, the current data may suggest consideration for potential biologi cal effects of PMF in the cardiovascular system. (C) 2000 Elsevier Science B.V. All rights reserved.