title: Ionizing radiation causes increased tau phosphorylation in primary neurons.
abstract: Radiotherapy is the major treatment modality for primary and metastatic brain tumors which involves the exposure of brain to ionizing radiation. Ionizing radiation can induce various detrimental pathophysiological effects in the adult brain, and Alzheimer's disease and related neurodegenerative disorders are considered to be late effects of radiation. In this study, we investigated whether ionizing radiation causes changes in tau phosphorylation in cultured primary neurons similar to that in Alzheimer's disease. We demonstrated that exposure to 0.5 or 2 Gy γ rays causes increased phosphorylation of tau protein at several phosphorylation sites in a time- and dose-dependent manner. Consistently, we also found ionizing radiation causes increased activation of GSK3β, c-Jun N-terminal kinase and extracellular signal-regulated kinase before radiation-induced increase in tau phosphorylation. Specific inhibitors of these kinases almost fully blocked radiation-induced tau phosphorylation. Our studies further revealed that oxidative stress plays an important role in ionizing radiation-induced tau phosphorylation, likely through the activation of c-Jun N-terminal kinase and extracellular signal-regulated kinase, but not GSK3β. Overall, our studies suggest that ionizing radiation may cause increased risk for development of Alzheimer's disease by promoting abnormal tau phosphorylation.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA; Yueyang Hospital and Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Wang
authors.forename: Scott
authors.initials: S
authors.lastname: Welford
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.forename: Xinglong
authors.initials: X
authors.lastname: Wang
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005260:Female; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects*; D010766:Phosphorylation / Q000502:physiology / Q000528:radiation effects; D011247:Pregnancy; D011839:Radiation, Ionizing; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism* / Q000528:radiation effects*
chemical_list: D016875:tau Proteins
keywords: ERK; GSK3β; JNK; ionizing radiation; oxidative stress; tau phosphorylation