Abstract | BACKGROUND AND PURPOSE: Ischemic/reperfusion neuronal injury is characterized by accumulation of reactive oxygen species and oxidative DNA damage, which can trigger cell death by various signaling pathways. Two of these modes of death include poly(ADP-ribose) polymerase 1-mediated death or p53- and Bax-mediated apoptosis. The present study tested the hypothesis that peroxiredoxin 2 (PRX2) attenuates DNA damage-mediated prodeath signaling using in vitro and in vivo models of ischemic injury. The impact of this peroxide scavenger on p53- and poly(ADP-ribose) polymerase 1-mediated ischemic death is unknown. METHODS: RESULTS: CONCLUSIONS: The promising therapeutic candidate PRX2 can clamp upstream DNA damage and efficiently inhibit multiple prodeath cascades operating in both parallel and interactive fashions.
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Authors | Rehana K Leak, Lili Zhang, Yumin Luo, Peiying Li, Haiping Zhao, Xiangrong Liu, Feng Ling, Jianping Jia, Jun Chen, Xunming Ji |
Journal | Stroke
(Stroke)
Vol. 44
Issue 4
Pg. 1124-34
(Apr 2013)
ISSN: 1524-4628 [Electronic] United States |
PMID | 23429506
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthracenes
- Bax protein, mouse
- Reactive Oxygen Species
- TP53 protein, human
- Tumor Suppressor Protein p53
- bcl-2-Associated X Protein
- pyrazolanthrone
- Peroxiredoxins
- Poly(ADP-ribose) Polymerases
- MAP Kinase Kinase 4
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Topics |
- Animals
- Anthracenes
(pharmacology)
- Apoptosis
- Brain Ischemia
(metabolism, pathology)
- Cells, Cultured
- DNA Damage
- Humans
- MAP Kinase Kinase 4
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- Neurons
(metabolism)
- Peroxiredoxins
(metabolism)
- Poly(ADP-ribose) Polymerases
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
- Reperfusion Injury
- Signal Transduction
- Tumor Suppressor Protein p53
(metabolism)
- bcl-2-Associated X Protein
(metabolism)
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