Document Detail


EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrocytes.
MedLine Citation:
PMID:  20444431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Astrocytes play an important role in protecting neurons during ischemia and reperfusion in the central nervous system. Although many studies have shown that oxygen-glucose deprivation (OGD) can induce astrocyte apoptosis, the role of PERK/eIF2 alpha/ATF4 integrated stress response (ISR) in astrocyte apoptosis mediated by oxygen-glucose-serum deprivation (OGSD)/restoration remains uncertain. Astrocytes were subjected to a combination of oxygen, glucose, and serum deprivation for 8h followed by restoration. Hoechst 33342 staining was performed to quantify apoptotic astrocytes and cell viability was assessed with Cell Counting Kit-8 (CCK8). Immunocytochemical analysis and Western blotting for some related molecules, including pancreatic ER stress kinase (PERK), p-PERK, eukaryotic initiation factor 2 alpha (eIF2 alpha), p-eIF2 alpha, activating transcription factor 4 (ATF4), caspase-12, were examined. Caspase activation and apoptosis were detected in neonatal rat astrocytes from spinal cord subjected to OGSD/restoration. We also observed an increase in cytoplasmic staining of p-eIF2 alpha in astrocytes (8h OGSD/15 min restoration) compared with that of non-treated cells. In addition, we found the sequential activation of PERK, eIF2 alpha, and ATF4 during OGSD/restoration by Western blotting. These results indicate that both the PERK/eIF2 alpha/ATF4 ISR and activation of caspase-12 may be involved in apoptosis of spinal cord astrocytes induced by OGSD/restoration.
Authors:
Ailiang Zhang; Jie Zhang; Peng Sun; Changjiang Yao; Changhui Su; Tao Sui; Hua Huang; Xiaojian Cao; Yingbin Ge
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-02
Journal Detail:
Title:  Neuroscience letters     Volume:  478     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-08-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  32-6     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
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MeSH Terms
Descriptor/Qualifier:
Activating Transcription Factor 4 / physiology
Animals
Animals, Newborn
Apoptosis*
Astrocytes / cytology*,  metabolism
Caspase 12 / physiology*
Cell Survival
Cells, Cultured
Culture Media, Serum-Free
Enzyme Activation
Eukaryotic Initiation Factor-2 / physiology*
Glucose / deficiency*
Oxygen / metabolism*
Rats
Rats, Sprague-Dawley
Spinal Cord / cytology*,  metabolism
eIF-2 Kinase / physiology
Chemical
Reg. No./Substance:
0/Atf4 protein, rat; 0/Casp12 protein, rat; 0/Culture Media, Serum-Free; 0/Eukaryotic Initiation Factor-2; 145891-90-3/Activating Transcription Factor 4; 50-99-7/Glucose; 7782-44-7/Oxygen; EC 2.7.10.-/PERK kinase; EC 2.7.11.1/eIF-2 Kinase; EC 3.4.22.-/Caspase 12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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