Disease relevance of Parp1

• These results indicated that PARP-1 plays a principal role in inducing mitochondrial impairment that ultimately leads to apoptosis of neurons after cerebral ischemia [1].
• These findings suggest that although blockade of PARP activity fully attenuates NMDA-induced PAR formation and loss of retinal ATP content, and improves the survival of select populations of ganglion cells, this approach does not provide full neuroprotection [2].
• These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation [3].
• BACKGROUND: Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury [4].
• To further study the mechanism of peroxynitrite toxicity to neurons we investigated the role of caspases and poly (ADP-ribose) polymerase (PARP) in this model system [5].

Psychiatry related information on Parp1

• CONCLUSIONS: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction [6].
• In this study the effect of Abeta 25-35 (25 microM) and non-Abeta component of Alzheimer's disease amyloid (NAC, 10 microM) on mChR-dependent signaling to PARP-1 was determined [7].

High impact information on Parp1

• We found that the CA1 tissue from hippocampus possesses an ADPRT activity that is dramatically stimulated by NO and attenuated by two different inhibitors of mono-ADPRT activity, phylloquinone and nicotinamide [8].
• Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus [8].
• Hepatocyte apoptosis, caspase activation, and poly (ADP-ribose) polymerase (PARP) cleavage, which are normally observed in response to both bile acids, were largely prevented after preincubation of hepatocytes with betaine [9].
• Caspase inhibition accelerates the loss of mitochondrial potential and shifts the mode of cell death to necrosis; inhibition of PARP with 3AB attenuates this effect of caspase inhibition [10].
• DNA strand breaks and associated activation of poly-ADP-ribose polymerase (PARP) and NAD depletion occur rapidly after exposure to homocysteine and precede mitochondrial dysfunction, oxidative stress, and caspase activation [10].

Chemical compound and disease context of Parp1

• 2. This study investigated the effect of the PARP-1 inhibitors 6(5H)-phenanthridinone and benzamide as well as that of benzoic acid, an inactive analogue of benzamide, on development of experimental allergic encephalomyelitis (EAE) in rats [11].
• We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target [12].
• Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage) [13].

Biological context of Parp1

• Recent reports have linked neuronal cell death by necrosis to poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation [2].
• The tripeptide protease inhibitor z-Val-Ala-Asp (zVAD) prevented PARP and lamin cleavage, DNA fragmentation, morphological changes, and cell detachment in irradiated EC [14].
• Poly(ADP-ribose) polymerase 1 (PARP-1) is the predominant NAD-dependent modifying enzyme in DNA repair, transcription, and apoptosis; its involvement in development has not been defined [15].
• In later gestation and postnatally, PARP-1 staining was primarily cytoplasmic and progressively restricted to a subset of cells, mainly bronchial epithelial and smooth muscle cells [15].
• In conclusion, levels of oxidative DNA damage and the DNA repair enzyme PARP-1 are increased in vessels after balloon injury [16].

Anatomical context of Parp1

• These apoptotic changes of mitochondria and the nucleus were attenuated by PARP-1 inhibitors, 1,5-dihydroxyisoquinoline and benzamide, and also by small interfering RNA specific for PARP-1 [1].
• Attenuation of neointima formation through the inhibition of DNA repair enzyme PARP-1 in balloon-injured rat carotid artery [16].
• Inhibition of PARP-1 attenuates neointima formation through inhibition of leukocyte infiltration and improvement of endothelial cell recovery after balloon injury [16].
• Co-localization of poly(ADPR)polymerase 1 (PARP-1) poly(ADPR)polymerase 2 (PARP-2) and related proteins in rat testis nuclear matrix defined by chemical cross-linking [17].
• Moreover, the association of pADPR and PARP-1 with the nuclear matrix (NM) has been reported, based on the poly(ADP-ribosyl)ation of nuclear matrix proteins (NMPs) [17].

Associations of Parp1 with chemical compounds

• Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only partial neuroprotection against NMDA-induced cell death in the rat retina [2].
• Inhibition of PARP-1 activity by 5-iodo-6-amino-1,2-benzopyrone in fetal rat lung explant culture did not affect SP-A and -B mRNA, but significantly increased SP-C mRNA [15].
• In the present article, by the use of DNA and protein cross-linking reactions, by cis-diamminedichloroplatinum II (cDDP) and sodium tetrathionate (NaTT) respectively, we present more evidences about the association of PARP-1, PARP-2, and PARPs related proteins with the NM [17].
• Western blot analysis of proteins was performed by probing immunoblots with antibodies against p53, bax and PARP (poly ADP-ribose polymerase) [18].
• We describe the involvement of poly(ADP-ribose)polymerase 1 and 2 (PARP-1 and -2) and poly(ADP-ribose)glycohydrolase (PARG) in the response of rat germinal cells to the action of the NO donors, 3-morpholino-sydnonimine (SIN-1) and spermine nonoate (SNO) [19].

Regulatory relationships of Parp1

• Caspase inhibition switches the mode of cell death induced by cyanide by enhancing reactive oxygen species generation and PARP-1 activation [20].

Other interactions of Parp1

• Caspase-9 and -3 were activated, causing cleavage of PARP, a hallmark of apoptosis and internucleosomal DNA fragmentation [21].
• Western blot analysis showed no change either on poly-ADP ribose polymerase (PARP) or p53 transcription factor in CCI and sham rats [22].
• Activation of intracellular caspases, manifest by proteolytic poly (ADP-ribose) polymerase (PARP) and lamin B cleavage, was maximal at 15 h after IR, concident with other indices of EC apoptosis, including oligonucleosomal DNA degradation, TUNEL immunostaining, and morphologic changes [14].
• Furthermore, inhibition of poly(ADP-ribosylation) prevented intranuclear localization of apoptosis-inducing factor and protected neurons from excitotoxic injury; and PARP-1 null fibroblasts were protected from oxidative stress-induced cell death [23].
• Furthermore, a large decrease of apoptotic bodies was associated with a significant drop of caspase and PARP-1 cleavages, suggesting that the protective effect of DP closely correlates with limitation of apoptosis expansion [24].

Analytical, diagnostic and therapeutic context of Parp1

• HI induced a marked increase in activated caspase-9, caspase-3 and PARP cleavage at 12 h to 7 days after HI in brain areas displaying TUNEL (+) cells [25].
• Immunohistochemistry for PARP-1 in Embryonic Day 18 rat lung showed predominantly nuclear staining in most cells [15].
• Furthermore, PARP inhibitors significantly decrease the ischemia-reperfusion-induced increase of lipid peroxidation, protein oxidation, single-strand DNA breaks, and the inactivation of respiratory complexes, which indicate a decreased mitochondrial ROS production in the reperfusion period [26].
• Purified germinal cell populations and rats of different age were used for activity-, immuno-, and Northern blot experiments, to determine at which level poly(ADPR)polymerase (PARP) is regulated at various stages of spermatogenesis [27].
• The DNA synthesis was due to de novo synthesis and not to DNA repair as a consequence of the initiation of apoptosis, determined by flow cytometry, and lack of proteolytic activation of PARP by caspase 3 [28].

References