Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis
| Autor: | Shihua Li, Suzanne Lam, Xiao-Jiang Li, Anna L. Cheng |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Programmed cell death Huntingtin Fluorescent Antibody Technique Apoptosis Cytochrome c Group Nerve Tissue Proteins DNA Fragmentation Transfection PC12 Cells Gene Expression Regulation Enzymologic Cell Line mental disorders Genetics Huntingtin Protein medicine Animals Humans RNA Messenger Nuclear protein Molecular Biology Genetics (clinical) Caspase Cell Nucleus biology Cytochrome c Caspase 1 Nuclear Proteins General Medicine Mitochondria Rats Up-Regulation nervous system diseases Cell biology Enzyme Activation Oxidative Stress Cell nucleus Huntington Disease medicine.anatomical_structure nervous system Biochemistry Caspases biology.protein Peptides Trinucleotide Repeat Expansion |
| Zdroj: | Human Molecular Genetics. 9:2859-2867 |
| ISSN: | 1460-2083 |
| DOI: | 10.1093/hmg/9.19.2859 |
| Popis: | Expansion of a polyglutamine repeat in huntingtin causes Huntington's disease (HD). Although full-length huntingtin is predominantly distributed in the cytoplasm, N-terminal fragments of huntingtin with expanded polyglutamine tracts are able to accumulate in the nucleus and kill neurons through apoptotic pathways. Transgenic mice expressing N-terminal mutant huntingtin show intranuclear huntingtin accumulation and develop progressive neurological symptoms. Inhibiting caspase-1 can prolong the survival of these HD mice. How intranuclear huntingtin is associated with caspase activation and apoptosis is unclear. Here we report that intranuclear huntingtin induces the activation of caspase-3 and the release of cytochrome c from mitochondria in cultured cells. As a result, cells expressing intranuclear huntingtin undergo apoptosis. We show that intranuclear huntingtin increases the expression of caspase-1, which may in turn activate caspase-3 and trigger apoptosis. We propose that the increased level of caspase-1 induced by intranuclear huntingtin contributes to HD-associated cell death. |
| Databáze: | OpenAIRE |
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