Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

被引：37

作者：

Chen, Jiann-Hwa ^{[1
,2
,3
]}

Kuo, Hsing-Chun ^{[4
,5
,6
]}

Lee, Kam-Fai ^{[7
]}

Tsai, Tung-Hu ^{[1
,8
,9
]}

机构：

[1] Natl Yang Ming Univ, Inst Tradit Med, Sch Med, Taipei 112, Taiwan

[2] Fu Jen Catholic Univ, Sch Med, Taipei 112, Taiwan

[3] Cathay Gen Hosp, Dept Emergency Med, Taipei 112, Taiwan

[4] Chang Gung Univ Sci & Technol, Dept Nursing, Chiayi 61363, Taiwan

[5] CGUST, Chron Dis & Hlth Promot Res Ctr, Chiayi 61363, Taiwan

[6] Chang Gung Univ Sci & Technol, Res Ctr Ind Human Ecol, Taoyuan 333, Taiwan

[7] Chang Gung Mem Hosp, Dept Pathol, Chiayi 61363, Taiwan

[8] Kaohsiung Med Univ, Sch Pharm, Coll Pharm, Kaohsiung 807, Taiwan

[9] Taipei City Hosp, Dept Educ & Res, Taipei 112, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2015年 / 16卷 / 06期

关键词：

ENDOPLASMIC-RETICULUM STRESS; CELL-DEATH; GLUCOSE DEPRIVATION; HYPOXIA-ISCHEMIA; NEONATAL-RAT; LIVER-INJURY; APOPTOSIS; MECHANISMS; STROKE; PATHOPHYSIOLOGY;

D O I：

10.3390/ijms160611873

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury.

引用

页码：11873 / 11891

页数：19

共 38 条

[1] Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12 [J].