Protecting intestinal epithelial cell number 6 against fission neutron irradiation through NF-κB signaling pathway.

The purpose of this paper is to explore the change of NF-κB signaling pathway in intestinal epithelial cell induced by fission neutron irradiation and the influence of the PI3K/Akt pathway inhibitor LY294002. Three groups of IEC-6 cell lines were given: control group, neutron irradiation of 4 Gy group, and neutron irradiation of 4 Gy with LY294002 treatment group. Except the control group, the other groups were irradiated by neutron of 4 Gy. LY294002 was given before 24 hours of neutron irradiation. At 6 h and 24 h after neutron irradiation, the morphologic changes, proliferation ability, apoptosis, and necrosis rates of the IEC-6 cell lines were assayed and the changes of NF-κB and PI3K/Akt pathway were detected. At 6 h and 24 h after neutron irradiation of 4 Gy, the proliferation ability of the IEC-6 cells decreased and lots of apoptotic and necrotic cells were found. The injuries in LY294002 treatment and neutron irradiation group were more serious than those in control and neutron irradiation groups. The results suggest that IEC-6 cells were obviously damaged and induced serious apoptosis and necrosis by neutron irradiation of 4Gy; the NF-κB signaling pathway in IEC-6 was activated by neutron irradiation which could protect IEC-6 against injury by neutron irradiation; LY294002 could inhibit the activity of IEC-6 cells.

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

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.

AduoLa Fuzhenglin down-regulates microwave-induced expression of ß1-adrenergic receptor and muscarinic type 2 acetylcholine receptor in myocardial cells of rats.

This paper is aimed to study the effect of ADL on expression of ß1-AR and M2-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ß1-AR and M2-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/(kg•d) ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/(kg•d) ADL groups than in microwave group. So we have a conclusion that the expression of ß1-AR and M2-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.

[Jak/STAT signaling pathway of IL-11 in the protection of intestinal epithelial cells from neutron radiation].

AIM: To explore the effect of IL-11 on the activation of Jak/STAT pathway and the expressions of Bax and Bcl-2 in the intestinal epithelial cells exposed to neutron radiation. METHODS: The BALB/c mice and IEC-6, irradiated by 4 Gy neutron with or without IL-11 treatment, served as in vivo and in vitro model seperately. The changes of the intestines, activity of Jak1 and STAT3 and expressions of Bax and Bcl-2 were observed by HE staining, Western blot, EMSA, immunohistochemistry and image analysis. RESULTS: (1)Mice exposed to neutron radiation showed severe intestinal damages and no obvious regeneration was seen. IL-11-treated mice had a larger number of cryptal epithelial cells and crypts. (2)Neutron radiation decreased the activities of Jak1 and STAT3, while IL-11 increased their activities. (3) Neutron radiation decreased the expression of Bax and didn't change the level of Bcl-2 in the murine intestine. IL-11 administration decreased the expression of Bax and increased that of Bcl-2. CONCLUSION: The mechanism of the intestinal protection of IL-11 in neutron irradiation might be that IL-11 stimulation triggered activation of Jak/STAT pathway, downregulated the expression of Bax and upregulated the expression of Bcl-2.