| Mediation of cell death by poly(ADP-ribose) polymerase-1. | |
| | |
MedLine Citation:
|
PMID: 15911329 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Poly(ADP-ribosyl)ation plays an important role in modulating the cellular response to stress. The extent of poly(ADP-ribosyl)ation, chiefly via the activation of the poly(ADP-ribose) polymerase-1 (PARP-1), correlates with the severity of genotoxic stress and this determines the cellular response. Under mild and moderate stress, it plays important roles in DNA processing and it participates in the proinflammatory/cellular defense via transcriptional regulation. However, severe stress following acute neuronal injury causes the overactivation of PARP-1, which results in unregulated poly(ADP-ribose) (PAR) synthesis and widespread neuronal cell death. Previously, this PARP-1-dependent cell death mechanism was manifest solely through necrosis, but apoptotic mechanisms are also evident. Poly(ADP-ribosyl)ation directly induces the nuclear translocation of apoptosis-inducing factor, which results in caspase-independent cell death significant in many neurodegenerative conditions. Further, the hydrolysis of PAR by poly(ADP-ribose) glycohydrolase (PARG) has a protective role, since the accumulation of PAR leads to cell death by apoptosis. Thus, PAR signaling, regulated by PARP-1 and PARG, mediates cell death. Accordingly, modulation of PAR synthesis or degradation through the targeting of PARP-1 or PARG holds particular promise in the treatment of conditions such as cancer, stroke, and Parkinson's disease. |
| | |
Authors:
|
David W Koh; Ted M Dawson; Valina L Dawson |
Related Documents
:
|
15862279 - Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin-induced... 11172589 - Potential role of caspase-3 and -9 in arsenic trioxide-mediated apoptosis in pci-1 head... 15911099 - Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia... 11886259 - The 3c protease activity of enterovirus 71 induces human neural cell apoptosis. 19410639 - Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in j774a.1 murine ... 20640889 - Caspase-3 triggers a tpck-sensitive protease pathway leading to degradation of the bh3-... 8982979 - An approach to study molecular mechanisms involved in cytokine-induced anorexia. 2109339 - Effect of thyrotropin-releasing hormone on immune functions of peripheral blood mononuc... 17943119 - Manipulation of host-cell pathways by bacterial pathogens. |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Pharmacological research : the official journal of the Italian Pharmacological Society Volume: 52 ISSN: 1043-6618 ISO Abbreviation: Pharmacol. Res. Publication Date: 2005 Jul |
Date Detail:
|
Created Date: 2005-05-24 Completed Date: 2005-08-25 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8907422 Medline TA: Pharmacol Res Country: England |
Other Details:
|
Languages: eng Pagination: 5-14 Citation Subset: IM |
Affiliation:
|
Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* Apoptosis Inducing Factor Brain Injuries / drug therapy Enzyme Inhibitors / therapeutic use Flavoproteins / physiology Glycoside Hydrolases / physiology Humans Membrane Proteins / physiology NF-kappa B / physiology Necrosis Neurons / pathology Parkinson Disease / drug therapy Poly(ADP-ribose) Polymerases / antagonists & inhibitors, physiology* Stroke / drug therapy |
| Chemical | |
Reg. No./Substance:
|
0/AIFM1 protein, human; 0/Apoptosis Inducing Factor; 0/Enzyme Inhibitors; 0/Flavoproteins; 0/Membrane Proteins; 0/NF-kappa B; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.143/poly ADP-ribose glycohydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Interaction of wogonin with bovine serum albumin.
Next Document: Poly(ADP-ribosyl)ation and stroke.