Poly(ADP-ribose) (PAR) polymer is a death signal
Johns Hopkins University · Johns Hopkins Medicine · +8 more institutions
Abstract
Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various of models of cellular injury. Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation of PAR polymer by poly(ADP-ribose) glycohydrolase (PARG) or phosphodiesterase 1 prevents PAR polymer-induced cell death. PARP-1-dependent, NMDA excitotoxicity of cortical neurons is reduced by neutralizing antibodies to PAR and by overexpression of PARG. Neuronal cultures with reduced levels of PARG are more sensitive to NMDA excitotoxicity than WT cultures. Transgenic mice…
Citation impact
- FWCI
- 17.62
- Percentile
- 100%
- References
- 35
Authors
14- SAShaida A. AndrabiCorresponding
Johns Hopkins University, Johns Hopkins Medicine, Institute of Pathology Celle
- NSNo Soo Kim
Johns Hopkins University, Institute of Pathology Celle
- SYSeong-Woon Yu
Johns Hopkins University, Institute of Pathology Celle, Michigan State University
- HWHongmin Wang
University of Maryland, Baltimore, Johns Hopkins University, Institute of Pathology Celle, University of Baltimore
- DWDavid W. Koh
Johns Hopkins University, Institute of Pathology Celle
Topics & keywords
- Poly ADP ribose polymerase
- Programmed cell death
- Apoptosis
- Excitotoxicity
- Chemistry
- Cell biology
- Biology
- Molecular biology
- Good health and well-being