Role of endoplasmic reticulum stress via the PERK signaling pathway in brain injury from status epilepticus.
Endoplasmic reticulum (ER) stress may play a role in status epilepticus (SE). Sprague-Dawley rats were randomized into three groups: control (saline), SE (pentylenetetrazol), and dentate gyrus (DG), pretreated with 2-deoxy-D-glucose (2-DG). Expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor 2α (eIF2α), and protein kinase RNA-like ER kinase (PERK) were determined. CHOP messenger RNA (mRNA) and protein expression levels in SE group were significantly increased as compared to the control group (P < 0.0001), and significantly decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated eIF-2α protein expression level in SE group was significantly increased as compared to the control group (P < 0.0001) and significantly decreased in DG group as compared to the SE group (P < 0.0001). GRP messenger RNA expression levels and protein levels in SE group was significantly increased as compared to the control group (P < 0.0001) and significantly decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated PERK protein expression level in SE group was significantly increased as compared to the control group (P < 0.0001), and significantly decreased in DG group as compared to the SE group (P < 0.0001) at the time of 12 and 24 h. Our results suggest that brain injury from SE might involve ER stress via the pro-apoptotic PERK-eIF2α-CHOP signaling pathway.
Department of Neurology, Nanjing Children's Hospital, Nanjing Medical University, No. 72, Guangzhou Road, Gu Lou District, Nanjing, Jiangsu, 210008, People's Republic of China, drchenj@yeah.net.
Jing
J
Chen
Guo
G
Zheng
Hu
H
Guo
Zhong-Nan
ZN
Shi
D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013226:Status Epilepticus / Q000150:complications / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP