Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain.

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Abstract Text:

M F Poitras,D W Koh,S-W Yu,S A Andrabi,A S Mandir,G G Poirier,V L Dawson,T M Dawson,M F Poitras,D W Koh,S-W Yu,S A Andrabi,A S Mandir,G G Poirier,V L Dawson,T M Dawson,

Poly(ADP-ribose) polymerases (PARPs) are members of a family of enzymes that utilize nicotinamide adenine dinucleotide (NAD(+)) as substrate to form large ADP-ribose polymers (PAR) in the nucleus. PAR has a very short half-life due to its rapid degradation by poly(ADP-ribose) glycohydrolase (PARG). PARP-1 mediates acute neuronal cell death induced by a variety of insults including cerebral ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, and CNS trauma. While PARP-1 is localized to the nucleus, PARG resides in both the nucleus and cytoplasm. Surprisingly, there appears to be only one gene encoding PARG activity, which has been characterized in vitro to generate different splice variants, in contrast to the growing family of PARPs. Little is known regarding the spatial and functional relationships of PARG and PARP-1. Here we evaluate PARG expression in the brain and its cellular and subcellular distribution in relation to PARP-1. Anti-PARG (alpha-PARG) antibodies raised in rabbits using a purified 30 kDa C-terminal fragment of murine PARG recognize a single band at 111 kDa in the brain. Western blot analysis also shows that PARG and PARP-1 are evenly distributed throughout the brain. Immunohistochemical studies using alpha-PARG antibodies reveal punctate cytosolic staining, whereas anti-PARP-1 (alpha-PARP-1) antibodies demonstrate nuclear staining. PARG is enriched in the mitochondrial fraction together with manganese superoxide dismutase (MnSOD) and cytochrome C (Cyt C) following whole brain subcellular fractionation and Western blot analysis. Confocal microscopy confirms the co-localization of PARG and Cyt C. Finally, PARG translocation to the nucleus is triggered by NMDA-induced PARP-1 activation. Therefore, the subcellular segregation of PARG in the mitochondria and PARP-1 in the nucleus suggests that PARG translocation is necessary for their functional interaction. This translocation is PARP-1 dependent, further demonstrating a functional interaction of PARP-1 and PARG in the brain.

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Publishing Authors By Initials

MF Poitras,DW Koh,SW Yu,SA Andrabi,AS Mandir,GG Poirier,VL Dawson,TM Dawson,MF Poitras,DW Koh,SW Yu,SA Andrabi,AS Mandir,GG Poirier,VL Dawson,TM Dawson,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuroscience

VOLUME: 148

Page Numbers: 198-211

Journal Abbreviation: Neuroscience

ISSN: 0306-4522

DAY: 19

MONTH: 07

YEAR: 2007

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7605074

Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain.

AFFILIATION: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Broadway Research Building, 733 North Broadway, Suite 731, Baltimore, MD 21205, USA.

Country: United States

AGENCY: United States NINDS

GRANT: P01 NS039148-090005

ACRONYM: NS

MEDLINETA: Neuroscience

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Spatial and functional relationship between polyADP-ribose polymerase-1 and polyADP-ribose glycohydrolase in the brain Related Publications

• A novel role of the Batten disease gene CLN3: association with BMP synthesis.
• Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption.
• Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death.
• Bone morphogenetic proteins BMPs. Letter.
• Despite major challenges, autism research continues to offer hope.
• Epothilones in prostate cancer: review of clinical experience.
• Experimental spinal fusion with recombinant human bone morphogenetic protein-2 without decortication of osseous elements.
• Free radicals and neuronal cell death.
• Horse heart myoglobin catalyzes the H2O2-dependent oxidative dehalogenation of chlorophenols to DNA-binding radicals and quinones.
• Impaired navigation in drivers with Parkinson's disease.
• Impaired visual search in drivers with Parkinson's disease.
• Improving the efficiency of estimation in randomized trials of adaptive treatment strategies.
• Investigation of ligand interactions with human RXRalpha by hydrogen/deuterium exchange and mass spectrometry.
• MPTP and DSP-4 susceptibility of substantia nigra and locus coeruleus catecholaminergic neurons in mice is independent of parkin activity.
• Nasal cytology: a marker of clinically silent inflammation in patients with obstructive sleep apnea and a predictor of noncompliance with nasal CPAP therapy.
• Nucleophilic catalysis of hydrazone formation and transimination: implications for dynamic covalent chemistry.
• Nucleophilic catalysis of oxime ligation.
• Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain.
• Poly(ADP-ribose) (PAR) polymer is a death signal.
• Prototype misidentification makes conclusions about pathotype growth characteristics uncertain.
• Quantitative analytical methods in translation research.
• Resting state cortical connectivity reflected in EEG coherence in individuals with autism.
• Risk-adjusted cesarean rates: what risk factors for cesarean delivery are important to practicing obstetricians?
• Sources of stress and burnout in acute psychiatric care: inpatient vs. community staff.
• Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain.
• Spectroscopic investigations of intermediates in the reaction of cytochrome P450(BM3)-F87G with surrogate oxygen atom donors.
• The use of the Oxford hip and knee scores.
• Threading a peptide through a peptide: protein loops, rotaxanes, and knots.
• Time dependence in mixture toxicity with soft electrophiles: 1. Combined effects of selected SN2- and SNAr-reactive agents with a nonpolar narcotic.
• Treatment of natural infestations of the biting louse (Werneckiella equi) on horses using triflumuron, a benzoylurea derivative insect growth regulator.