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Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)O(2) injury.
J Neurochem. 2002 Jul; 82(1):19-29.JN

Abstract

Toxic reactive oxygen species (ROS) such as hydrogen peroxide, nitric oxide, superoxide, and the hydroxyl radical are generated in a variety of neuropathological conditions and cause significant DNA damage. We determined the effects of 3-aminobenzamide (AB), an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), on cell death in differentiated PC12 cells, a model of sympathetic neurons, after H(2) O(2) injury. Exposure to 0.5 mm H(2) O(2) resulted in a significant decrease in intracellular NAD(H), NADP(H), and ATP levels. This injury resulted in the death of 90% of the cells with significant necrosis early (2 h) after injury and increased apoptosis (12-24 h after injury), as measured by PS exposure and the presence of cytoplasmic oligonucleosomal fragments. Treatment with 2.5 mm AB restored pyridine nucleotide and ATP levels and ameliorated cell death (65% versus 90%) by decreasing the extent of both necrosis and apoptosis. Interestingly, we observed that H(2) O(2) -induced injury caused a delayed cell death exhibiting features of apoptosis but in which caspase-3 like activity was absent. Moreover, pretreatment with AB restored caspase-3-like activity. Our results suggest that apoptosis and necrosis are both triggered by PARP overactivation, and that maintenance of cellular energy levels after injury by inhibiting PARP shifts cell death from necrosis to apoptosis.

Authors+Show Affiliations

Department of Anatomy and Neurosciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0652, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12091461

Citation

Cole, Kasie K., and J Regino Perez-Polo. "Poly(ADP-ribose) Polymerase Inhibition Prevents Both Apoptotic-like Delayed Neuronal Death and Necrosis After H(2)O(2) Injury." Journal of Neurochemistry, vol. 82, no. 1, 2002, pp. 19-29.
Cole KK, Perez-Polo JR. Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)O(2) injury. J Neurochem. 2002;82(1):19-29.
Cole, K. K., & Perez-Polo, J. R. (2002). Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)O(2) injury. Journal of Neurochemistry, 82(1), 19-29.
Cole KK, Perez-Polo JR. Poly(ADP-ribose) Polymerase Inhibition Prevents Both Apoptotic-like Delayed Neuronal Death and Necrosis After H(2)O(2) Injury. J Neurochem. 2002;82(1):19-29. PubMed PMID: 12091461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)O(2) injury. AU - Cole,Kasie K, AU - Perez-Polo,J Regino, PY - 2002/7/2/pubmed PY - 2002/8/6/medline PY - 2002/7/2/entrez SP - 19 EP - 29 JF - Journal of neurochemistry JO - J Neurochem VL - 82 IS - 1 N2 - Toxic reactive oxygen species (ROS) such as hydrogen peroxide, nitric oxide, superoxide, and the hydroxyl radical are generated in a variety of neuropathological conditions and cause significant DNA damage. We determined the effects of 3-aminobenzamide (AB), an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), on cell death in differentiated PC12 cells, a model of sympathetic neurons, after H(2) O(2) injury. Exposure to 0.5 mm H(2) O(2) resulted in a significant decrease in intracellular NAD(H), NADP(H), and ATP levels. This injury resulted in the death of 90% of the cells with significant necrosis early (2 h) after injury and increased apoptosis (12-24 h after injury), as measured by PS exposure and the presence of cytoplasmic oligonucleosomal fragments. Treatment with 2.5 mm AB restored pyridine nucleotide and ATP levels and ameliorated cell death (65% versus 90%) by decreasing the extent of both necrosis and apoptosis. Interestingly, we observed that H(2) O(2) -induced injury caused a delayed cell death exhibiting features of apoptosis but in which caspase-3 like activity was absent. Moreover, pretreatment with AB restored caspase-3-like activity. Our results suggest that apoptosis and necrosis are both triggered by PARP overactivation, and that maintenance of cellular energy levels after injury by inhibiting PARP shifts cell death from necrosis to apoptosis. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/12091461/Poly_ADP_ribose__polymerase_inhibition_prevents_both_apoptotic_like_delayed_neuronal_death_and_necrosis_after_H_2_O_2__injury_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2002&volume=82&issue=1&spage=19 DB - PRIME DP - Unbound Medicine ER -