Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization
| Autor: | Christopher A. Ross, J. Timothy Greenamyre, Solomon H. Snyder, Joseph F. Lawler, Alan H. Sharp, Gordon W. Wiegand, Jillian K. Cooper, Akira Sawa, Russell L. Margolis |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Programmed cell death Huntingtin Adolescent Glutamine Cell Apoptosis Mitochondrion Biology General Biochemistry Genetics and Molecular Biology Trinucleotide Repeats medicine Humans Lymphocytes Cyanides Caspase 3 Depolarization General Medicine Hematopoietic Stem Cells Staurosporine Molecular biology Mitochondria Cell biology Enzyme Activation Huntington Disease medicine.anatomical_structure Caspases Intracellular |
| Zdroj: | Nature Medicine. 5:1194-1198 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin1. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues2, so abnormalities outside the brain might be expected. Although involvement of nuclei3,4,5,6,7 and mitochondria8,9,10,11,12,13,14 in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains10,11,12,13; mitochondria are organelles that regulates apoptotic cell death15,16. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats. |
| Databáze: | OpenAIRE |
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