Comparison of effects on APP processing and cell death between RF-EMF and Ionizing radiation

Abstract

Alzheimer’s disease (AD) is a brain disorder that causes problems with memory, thinking and behavior. AD has a steady increase in the incidence of elderly people aged 65 years and older. In this study, the effect of LTE (Long term evolution) RF-EMF (1.745 GHz) on amyloid precursor protein (APP) processing was examined, because currently, the spread of LTE mobile communication network has increased. In vitro experiments of APP processing and cell death for determining effect of 1.745 GHz RF-EMF at specific absorption rate of 8 W/kg for 24 hrs were performed. For this purpose, HT22 mouse hippocampus cells and 7w-PSML cells, which overexpressed wild type human APP and the mutant presenilin-1 on CHO cells, were used. These cell lines have generally been used in vitro cellular models for neurodegenerative brain disorder like AD. Theses cells were exposed to 1.745 GHz RF-EMF at SAR of 8 W/kg for 24 hours or γ-radiation (IR) at 5 or 10 Gy. IR exposure was used as a positive control. IR exposure significantly increased the expression of BACE1 (β-secretase) in both HT22 and 7w-PSML cells, but IR did not show any changes on the expression of ADAM10 (α-secretase). Amyloidogenic APP processing product, CTFβ (C-terminal fragment β) was decreased after IR in HT22 cells, because of decreased expression of APP. Next experiments were performed whether IR affects APP expression via protein level or mRNA level. and were found that protein level of APP, not mRNA level, was decreased by IR. Indeed, cycloheximide treatment revealed that IR reduced protein half-life of APP in both HT22 and 7w-PSML cells. In the case of RF-EMF exposure, there were no significant changes on expressions of APP, BACE1 and ADAM10 as well as expression of CTFβ were observed. 7w-PSML cells showed resistant to IR than HT22 cells, because of higher expression of APP protein. The expression of apoptotic markers, such as cleaved PARP and cleaved caspase-3, after IR were significantly increased in both HT22 and 7w-PSML cells. RF-EMF slightly increased the expression levels of cell death markers, however, when we detected the cell death number, it was similar between control and RF-EMF exposure. IR exposure induced changes of the expression of APP, BACE1, CTFβ, but not ADAM10. IR affected protein level of APP, but not mRNA level. APP overexpressed cells such as 7w-PSML showed more resistant to IR than HT22 cells. Exposure of 8 W/kg LTE type RF-EMF did not induce any significant changes of APP processing and cell death.;최근 스마트폰 사용량이 늘어남에 따라, 전자파 사용에 따른 신체에 영향을 미칠 수도 있다는 우려 또한 함께 늘어나고 있다. 스마트폰에서 방출되는 전자파는 머리 부분인 뇌에 가장 많이 흡수될 것이고, 이 전자파에 어떤 변화가 유발될지에 대해 많은 실험들이 행해졌는데, 그 중 신경퇴행성 뇌 질환인 알츠하이머 질병을 대상으로 많은 실험이 진행되었다. 이 알츠하이머는 점진적으로 신경이 퇴행되는 질병으로, 이성적으로 사고가 어려워지고 읽고 쓰기 또한 어려워 지면서 일상적인 것들 또한 어려워지게 된다. 하지만 이 질병의 경우 정확한 원인이나 치료 방법이 밝혀지지 않았다. 여러 가설 중에선 아밀로이드 가설을 택하여 실험을 진행하였다. 동물 실험 부분에선, 알츠하이머 모델 쥐를 이용하여 전자파에 노출되는 기간이나 세기 등에 차이를 두고 여러 실험을 하였고, 오랜 기간에 노출된 쥐들에게서, 공간적 인지 기능이 개선되거나 알츠하이머의 대표적인 병변 증상인 아밀로이드 베타가 감소했다는 것을 확인한 바가 있다. 선행 연구에 의해서는 알츠하이머 모델 쥐를 전자파에 오랜 기간 동안 노출시켰을 때, 인지 기능이 개선된 결과를 보였다. 같은 조건하에 짧은 기간 동안 노출된 쥐에게서는 차이를 확인하기가 어려웠다. 이 실험에서는, HT22 세포와 7w-PSML 세포를 이용하여 LTE-RF-EMF를 SAR 8 W/kg로 24시간동안 노출시킨 후 실험을 진행하였다. 이 실험에서는 전자파에 의한 변화가 확인되지 않았기에, 짧은 기간의 노출로는 변화를 유발되지 않았다는 결론을 얻었다.