Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death.
J Cell Biol
; 165(3): 347-56, 2004 May 10.
Article
in En
| MEDLINE
| ID: mdl-15123740
ABSTRACT
Recent studies have suggested that neuronal death in Alzheimer's disease or ischemia could arise from dysfunction of the endoplasmic reticulum (ER). Although caspase-12 has been implicated in ER stress-induced apoptosis and amyloid-beta (Abeta)-induced apoptosis in rodents, it is controversial whether similar mechanisms operate in humans. We found that human caspase-4, a member of caspase-1 subfamily that includes caspase-12, is localized to the ER membrane, and is cleaved when cells are treated with ER stress-inducing reagents, but not with other apoptotic reagents. Cleavage of caspase-4 is not affected by overexpression of Bcl-2, which prevents signal transduction on the mitochondria, suggesting that caspase-4 is primarily activated in ER stress-induced apoptosis. Furthermore, a reduction of caspase-4 expression by small interfering RNA decreases ER stress-induced apoptosis in some cell lines, but not other ER stress-independent apoptosis. Caspase-4 is also cleaved by administration of Abeta, and Abeta-induced apoptosis is reduced by small interfering RNAs to caspase-4. Thus, caspase-4 can function as an ER stress-specific caspase in humans, and may be involved in pathogenesis of Alzheimer's disease.
Full text:
1
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
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Apoptosis
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Oxidative Stress
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Caspases
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Endoplasmic Reticulum
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Nerve Degeneration
Limits:
Humans
Language:
En
Journal:
J Cell Biol
Year:
2004
Type:
Article
Affiliation country:
Japan