title: Increased Expression of Caspase-12 After Experimental Subarachnoid Hemorrhage.
abstract: Convincing evidences have proved that apoptosis plays a vital role in the pathogenesis of early and delayed brain injury following subarachnoid hemorrhage (SAH). Recently, a novel caspase-12-mediated apoptotic pathway has been reported to be induced by excess endoplasmic reticulum (ER) stress. Extensive protein damage occurs after SAH, which may trigger ER stress-associated apoptotic pathway. Thus, we hypothesized that caspase-12, as the major molecular marker of this novel apoptotic pathway, may be activated and involved in the pathogenesis of apoptotic injury after SAH. This study sought to investigate the changes of caspase-12 expressions in both in vitro and in vivo SAH models. Western blot analysis found significantly increased protein expressions of both pro- and active forms of caspase-12 after SAH. Quantitative real-time PCR and immunohistochemistry assays confirmed elevated caspase-12 level after SAH in vivo. Further, double immunofluorescence staining revealed obvious caspase-12 over-expression in both cortical neurons and astrocytes. Moreover, immunofluorescent co-staining in vivo demonstrated that neural cells with high immunoreactivity of caspase-12 also expressed caspase-3, and dual-immunofluorescent staining for caspase-12 and TUNEL in vitro showed that TUNEL-positive cells were more likely to exhibit higher caspase-12 immunoreactivity, indicating a potential contribution of caspase-12 activation to apoptosis in SAH. Collectively, our results showed significant upregulation of caspase-12 expression after experimental SAH. These findings also offer important implications for further investigations of the therapeutic potential of caspase-12 associated apoptosis in SAH.
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi Province, China.
authors.forename: Li-Tian
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
authors.forename: Ding-Ding
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China. hang_neurosurgery@163.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology
chemical_list: D034961:Antigens, Nuclear; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C546339:Rbfox3 protein, rat; D053454:Caspase 12
keywords: Apoptosis; Caspase-12; Caspase-3; Endoplasmic reticulum stress; Subarachnoid hemorrhage