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Cell cycle activation linked to neuronal cell death initiated by DNA damage.
- Source :
-
Neuron [Neuron] 2004 Feb 19; Vol. 41 (4), pp. 549-61. - Publication Year :
- 2004
-
Abstract
- Increasing evidence indicates that neurodegeneration involves the activation of the cell cycle machinery in postmitotic neurons. However, the purpose of these cell cycle-associated events in neuronal apoptosis remains unknown. Here we tested the hypothesis that cell cycle activation is a critical component of the DNA damage response in postmitotic neurons. Different genotoxic compounds (etoposide, methotrexate, and homocysteine) induced apoptosis accompanied by cell cycle reentry of terminally differentiated cortical neurons. In contrast, apoptosis initiated by stimuli that do not target DNA (staurosporine and colchicine) did not initiate cell cycle activation. Suppression of the function of ataxia telangiectasia mutated (ATM), a proximal component of DNA damage-induced cell cycle checkpoint pathways, attenuated both apoptosis and cell cycle reentry triggered by DNA damage but did not change the fate of neurons exposed to staurosporine and colchicine. Our data suggest that cell cycle activation is a critical element of the DNA damage response of postmitotic neurons leading to apoptosis.
- Subjects :
- Animals
Apoptosis drug effects
Ataxia Telangiectasia Mutated Proteins
Cell Cycle drug effects
Cell Cycle Proteins
Cells, Cultured
Colchicine pharmacology
DNA Damage drug effects
DNA-Binding Proteins
Etoposide pharmacology
Female
Homocysteine pharmacology
Male
Methotrexate pharmacology
Mice
Nerve Degeneration metabolism
Neurons drug effects
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases genetics
Rats
Staurosporine pharmacology
Tumor Suppressor Proteins
Apoptosis genetics
Cell Cycle genetics
DNA Damage genetics
Nerve Degeneration genetics
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0896-6273
- Volume :
- 41
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 14980204
- Full Text :
- https://doi.org/10.1016/s0896-6273(04)00017-0