Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice.
Neuroscience
; 118(2): 491-9, 2003.
Article
in En
| MEDLINE
| ID: mdl-12699784
ABSTRACT
We sought to clarify the involvement of caspase-12, a representative molecule related to endoplasmic reticulum (ER) stress-induced cell-death signaling pathways, in neuronal death resulting from ischemia/reperfusion in mice. Transient focal cerebral ischemia (1 h) was produced by intraluminal occlusion of the middle cerebral artery (MCA). We assessed the expression patterns of caspase-12, Bip/GRP78, an ER-resident molecular chaperone whose expression serves as a good marker of ER stress, and caspase-7 by Western blotting and/or immunohistochemistry. Double-fluorescent staining of caspase-12 immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) method was performed to clarify the involvement of caspase-12 in cell death. We confirmed that ER stress was induced during reperfusion in our model, as witnessed by up-regulated Bip/GRP78 expression in the MCA territory. Western blot analysis revealed that caspase-12 activation occurred at 5-23 h of reperfusion, and immunoreactivity for caspase-12 was enhanced mainly in striatal neurons on the ischemic side at the same time points. We found the co-localization of caspase-12 immunoreactivity and DNA fragmentation detectable by the TUNEL method. We did not detect the presence of caspase-7 in the ER fraction at the period of caspase-12 cleavage. Our results imply that cerebral ischemia/reperfusion induces ER stress and that caspase-12 activation concurred with ER stress. Caspase-12 seems to be involved in neuronal death induced by ischemia/reperfusion. Caspase-7 is not likely to contribute to the cleavage of caspase-12 in our experimental model.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Physiological
/
Apoptosis
/
Caspases
/
Infarction, Middle Cerebral Artery
/
Endoplasmic Reticulum
/
Heat-Shock Proteins
Type of study:
Etiology_studies
/
Prognostic_studies
Language:
En
Journal:
Neuroscience
Year:
2003
Document type:
Article
Affiliation country:
Japan