title: RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway.
abstract: In the present study, we investigated whether Raf-1 kinase inhibitory protein (RKIP) is important for neural cell apoptosis induced by microwave exposure and explored the role of MEK/ERK/CREB pathway regulated by RKIP in the apoptosis. Differentiated PC12 cells were exposed to continuous microwave radiation at 2.856 GHz for 5 min with average power density of 30 mW/cm(2). RKIP sense and anti-sense recombinant plasmids were constructed and transfected into PC12 cells, respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay were used to detect cell apoptosis. The results showed that RKIP was downregulated after microwave exposure while the MEK/ERK/CREB signaling pathway was activated excessively. Moreover, the ratio of Bcl-2/Bax decreased, activity of caspase-3 increased, and thus apoptotic DNA fragmentation increased. RKIP overexpression significantly inhibited the phosphorylation of MEK, ERK, and CREB, while RKIP downregulation had the reverse effect. Furthermore, U0126 was found to antagonize the changes caused by RKIP downregulation after exposure to radiation. In conclusion, RKIP plays an important role in the neural cell apoptosis induced by microwave radiation, and the regulation of cell apoptosis by RKIP is partly through the MEK/ERK/CREB pathway. This suggests that RKIP may act as a key regulator of neuronal damage caused by microwave radiation.
authors.affiliation: Department of Experimental Pathology, Beijing Institute of Radiation Medicine, 27, Taiping Road,, Haidian District, Beijing, 100850, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zuo
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.forename: Dewen
authors.initials: D
authors.lastname: Wang
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Peng
authors.forename: Shuiming
authors.initials: S
authors.lastname: Wang
authors.forename: Yabing
authors.initials: Y
authors.lastname: Gao
authors.forename: Xinping
authors.initials: X
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Wang
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008872:Microwaves; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats
chemical_list: C550693:PEBP1 protein, rat; D049488:Phosphatidylethanolamine Binding Protein; D019908:Proto-Oncogene Proteins c-raf; C505410:Casp3 protein, rat; D053148:Caspase 3
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