Regulation of Autophagy Via PERK-eIF2α Effectively Relieve the Radiation Myelitis Induced by Iodine-125

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Nov 14

PMID 24223705

Citations 9

Authors

Zuozhang Yang

Yongqing Xu

Lei Xu

Giulio Maccauro

Barbara Rossi

Yanjin Chen

Hongjun Li

Jing Zhang

Hongpu Sun

Yihao Yang

Da Xu

Xuefeng Liu

Affiliations

Soon will be listed here.

Abstract

Radiation myelitis is the most serious complication in clinical radiotherapy for spinal metastases. We previously showed that (125)I brachytherapy induced apoptosis of spinal cord neurons accompanied by autophagy. In this study, we further investigated the mechanism by which (125)I radiation triggered autophagy in neural cells. We found that autophagy induced by (125)I radiation was involved in endoplasmic reticulum (ER) stress and mainly dependent on PERK-eIF2α pathway. The expressions of LC3II, ATG12 and PI3K were significantly suppressed in PERK knockout neural cells. Meanwhile, the expressions of phosphorylated-Akt s473 and caspase3/8 all significantly increased in neural cells transfected with a PERK siRNA and which enhanced apoptosis of neurons after (125)I radiation. The results were consistent with that by MTT and Annexin-FITC/PT staining. In animal model of banna pigs with radiation myelitis caused by (125)I brachytherapy, we have successfully decreased PERK expression by intrathecal administration of the lentivirus vector. The apoptosis rate was significantly higher than that in control group and which deteriorated radiation myelitis of banna pigs. Thus, autophagy caused by (125)I radiation was mainly as an attempt of cell survival at an early stage, but it would be a self-destructive process and promoted the process of apoptosis and necrosis radiated by (125)I for more than 72 hours. The study would be useful and helpful to maximize efficiency of radiation therapy in clinical therapy.

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