Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage

Inna I. Kruman, Robert P. Wersto, Fernando Cardozo-Pelaez, Lubomir Smilenov, Sic L. Chan, Francis J. Chrest, Roland Emokpae, Myriam Gorospe, Mark P. Mattson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)549-561
Number of pages13
JournalNeuron
Volume41
Issue number4
DOIs
StatePublished - Feb 19 2004

Fingerprint

DNA Damage
Cell Cycle
Cell Death
Apoptosis
Neurons
Staurosporine
Colchicine
Ataxia Telangiectasia
Homocysteine
Etoposide
Cell Cycle Checkpoints
Methotrexate
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kruman, I. I., Wersto, R. P., Cardozo-Pelaez, F., Smilenov, L., Chan, S. L., Chrest, F. J., ... Mattson, M. P. (2004). Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage. Neuron, 41(4), 549-561. https://doi.org/10.1016/S0896-6273(04)00017-0

Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage. / Kruman, Inna I.; Wersto, Robert P.; Cardozo-Pelaez, Fernando; Smilenov, Lubomir; Chan, Sic L.; Chrest, Francis J.; Emokpae, Roland; Gorospe, Myriam; Mattson, Mark P.

In: Neuron, Vol. 41, No. 4, 19.02.2004, p. 549-561.

Research output: Contribution to journalArticle

Kruman, II, Wersto, RP, Cardozo-Pelaez, F, Smilenov, L, Chan, SL, Chrest, FJ, Emokpae, R, Gorospe, M & Mattson, MP 2004, 'Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage', Neuron, vol. 41, no. 4, pp. 549-561. https://doi.org/10.1016/S0896-6273(04)00017-0
Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ et al. Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage. Neuron. 2004 Feb 19;41(4):549-561. https://doi.org/10.1016/S0896-6273(04)00017-0
Kruman, Inna I. ; Wersto, Robert P. ; Cardozo-Pelaez, Fernando ; Smilenov, Lubomir ; Chan, Sic L. ; Chrest, Francis J. ; Emokpae, Roland ; Gorospe, Myriam ; Mattson, Mark P. / Cell Cycle Activation Linked to Neuronal Cell Death Initiated by DNA Damage. In: Neuron. 2004 ; Vol. 41, No. 4. pp. 549-561.
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