Activation of VEGF/Flk-1-ERK Pathway Induced Blood–Brain Barrier Injury After Microwave Exposure

Abstract

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

Cecropin A Modulates Tight Junction-Related Protein Expression and Enhances the Barrier Function of Porcine Intestinal Epithelial Cells by Suppressing the MEK/ERK Pathway

“…In addition, previous studies have also showed that MEK/ERK inhibition may induce upregulation of TJs in undifferentiated cells, such as embryonic stem cells, intestinal epithelial cells (IEC-6, caco-2) or tumor cells [ 27 , 28 ]. Similarly, ERK activation may induce blood–brain barrier injury [ 29 ]. The related physiological processes are regulated by the transcriptional factors downstream of ERK.…”

EUROPAEM EMF Guideline 2016 for the prevention, diagnosis and treatment of EMF-related health problems and illnesses

“…This early insight has been corroborated by recent studies on various transmitter receptors in the brain such as N-methyl-D-aspartate receptors, dopamine and serotonin receptors (e.g. [148][149][150][151]. Some of these more recent studies also reported frequency window effects as well as intensity window effects on the neurodevelopment in the rat (152).…”

VEGF promotes cartilage angiogenesis by phospho-ERK1/2 activation of Dll4 signaling in temporomandibular joint osteoarthritis caused by chronic sleep disturbance in Wistar rats

“…As vascular invasion is suggested to be an early mechanism for turning cartilage into bone, these VEGF-expressing chondrocytes may promote the destruction of cartilage. However, angiogenic activity is not only determined by VEGF; p-ERK1/2 also stimulates angiogenesis [28]. Moreover, the Dll4-Notch signaling pathway is absolutely required for normal vascular development [29], and the perichondrial layer of the MCC is rich in both Notch ligands and various downstream facilitators of Notch signaling [30].…”