title: Down-regulation of GRP78 enhances apoptosis via CHOP pathway in retinal ischemia-reperfusion injury.
abstract: Ischemia/reperfusion (I/R) injury is the main cause of retinal apoptosis. But the mechanism remains elusive. During I/R injury, the intracellular calcium levels increase, resulting in the generation of reactive oxygen species, which have been shown to cause endoplasmic reticulum (ER) stress. However, little is known about the correlation between apoptosis and ER stress in retinal I/R injury. In the present study, we demonstrated that ER stress was activated in the retina of rat I/R models. The transcriptional expression of ER stress-associated molecules, glucose-regulated protein-78 (GRP78) and C/EBP-homologous protein (CHOP) were significantly increased in I/R retinas in a time-dependent manner. Partial inhibition of the endogenous expression of GRP78 with antisense oligonucleotide resulted in significant retinal damage and apoptosis in I/R injury rats. Also, the transcriptional expression of CHOP was persistently increased. Our findings indicate that ER stress may play a critical role in I/R injury induced retinal damage, and GRP78 may exert anti-apoptotic actions in I/R retina. Importantly, the persistent high expression of CHOP might serve as a possible mechanism that contributes to the enhanced the I/R-induced apoptosis after GRP78 down-regulation. These results may provide insight into the pathology of retinal I/R injury.
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Boya Eye Hospital, Changsha 410001, China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, China. Electronic address: luoshengt57@163.com.
authors.forename: Luosheng
authors.initials: L
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
keywords: Antisense-oligonucleotide; Apoptosis; CHOP; Endoplasmic reticulum stress; GRP78; Retinal ischemia reperfusion