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PMID: 15123740 Published · ppublish English Journal Article

Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death.

The Journal of cell biology ·Vol. 165 ·No. 3 ·2004-05-10 ·Pages 347-56

Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, Manabe T, Yamagishi S, Bando Y, Imaizumi K, Tsujimoto Y, Tohyama M

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.

MeSH Terms
Amyloid beta-Peptides/toxicity Apoptosis/drug effects,physiology Caspases/genetics,metabolism Caspases, Initiator Down-Regulation/genetics Endoplasmic Reticulum/enzymology HSP70 Heat-Shock Proteins/metabolism HeLa Cells Humans Immunohistochemistry Intracellular Membranes/enzymology Membrane Proteins/metabolism Nerve Degeneration/enzymology,pathology,physiopathology Neurodegenerative Diseases/enzymology,physiopathology Oxidative Stress/drug effects,physiology Proto-Oncogene Proteins c-bcl-2/metabolism RNA Interference Signal Transduction/physiology
Chemicals
Amyloid beta-Peptides HSP70 Heat-Shock Proteins Membrane Proteins Proto-Oncogene Proteins c-bcl-2 glucose-regulated proteins CASP4 protein, human Caspases Caspases, Initiator
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hitomi Junichi
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Katayama Taiichi
Eguchi Yutaka
Kudo Takashi
Taniguchi Manabu
Koyama Yoshihisa
Manabe Takayuki
Yamagishi Satoru
Bando Yoshio
Imaizumi Kazunori
Tsujimoto Yoshihide
Tohyama Masaya
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200310015
Published
2004-05-10
Epub
2004-00-03
Pages
347-56
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172196
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200310015 PMC Full Text View journal details
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