Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.4.2.30 (PARP)
13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.
...
PMID:Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum. 135 80

An endogenous ADP-ribosyltransferase is present in the cytosolic fraction of human platelets. Agents known to release nitric oxide activated this ADP-ribosylation reaction in a cGMP-independent fashion. This enzymatic activity was further enhanced by the addition of NADPH to the platelet cytosolic fraction. Interestingly, NADPH was unable to replace DTT, which has been described as an essential cofactor. Our results indicate that NADPH is a stimulatory factor of the endogenous ADP-ribosylation reaction. NADPH shifts the dose-response curve of NO to the left and possibly increases, in this way, the ADP-ribosylation reaction under physiological conditions.
...
PMID:NADPH: a stimulatory cofactor for nitric oxide-induced ADP-ribosylation reaction. 154 Jan 62

An ubiquitous biochemical pathway known to synthesize nitric oxide (NO) from L-arginine has been identified in many cell types. Recent studies indicate that besides activating soluble guanylate cyclase NO is likely to have effects unrelated to the known signal transduction pathway. Activation of the soluble NO synthase stimulates an endogenous ADP-ribosylation of a predominant 39 kDa protein, known to be activated by NO releasing agents. This is demonstrated using the cytosolic fraction of rat cerebellum and HL-60 cells. The ADP-ribosylation is suppressed by the known NO synthase inhibitors N-nitro-L-arginine and N-methyl-L-arginine. These observations indicate that NO derived from its physiological precursor L-arginine activates an endogenous ADP-ribosyltransferase.
...
PMID:L-arginine stimulates an endogenous ADP-ribosyltransferase. 190 40

A novel ADP-ribosyltransferase is present in the cytosolic fraction of various cells. The kinetic behavior and physical properties of this enzyme's activity are clearly distinguished from other known cytosolic ADP-ribosyltransferases. Agents that release nitric oxide, such as sodium nitroprusside, greatly stimulated this activity, although this effect was dependent on the presence of intact thiol groups. Dithiothreitol, reduced glutathione, or cysteine was needed for activation of the enzyme, while N-ethylmaleimide inhibited enzyme activity. High concentrations of phosphate had a slight stimulatory effect, while high concentrations of sodium chloride and thiocyanate were inhibitory. ATP also inhibited this activity. This cytosolic ADP-ribosyltransferase is clearly distinguished from other known and characterized cytosolic transferases. Its activation by biologically active nitric oxide suggests an important role for this enzymatic activity.
...
PMID:Properties of a novel nitric oxide-stimulated ADP-ribosyltransferase. 211 69

Sodium nitroprusside is a vasodilator and an inhibitor of platelet activation. It is thought that these effects are mediated by the spontaneous release of nitric oxide and stimulation of cytosolic guanylate cyclase. We have found that sodium nitroprusside (5-200 microM) greatly increased a cytosolic ADP-ribosyltransferase that ADP-ribosylates a soluble 39-kDa protein. This activity causes the mono-ADP-ribosylation of the 39-kDa protein, since digestion with snake venom phosphodiesterase releases 5'-AMP. This enzyme is present in platelets, brain, heart, intestine, liver, and lung. The effect of sodium nitroprusside is not related to stimulation of soluble guanylate cyclase and the production of cyclic GMP because cyclic GMP, dibutyryl cyclic GMP, and 8-bromo-cyclic GMP are ineffective. 3-Morpholinosydnonimine (commonly known as SIN-1) (20-1000 micrograms/ml), another compound that acts through the spontaneous formation of nitric oxide as does sodium nitroprusside, also stimulates ADP-ribosylation of the 39-kDa protein. Hemoglobin, which binds nitric oxide, inhibits sodium nitroprusside's activation of the cytosolic ADP-ribosyltransferase. These studies demonstrate a novel action of nitric oxide related to the activation of an endogenous ADP-ribosyltransferase. The physiological role of this ADP-ribosylation needs further exploration.
...
PMID:Activation of a cytosolic ADP-ribosyltransferase by nitric oxide-generating agents. 254 78

Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an early response of cells exposed to DNA-damaging compounds such as nitric oxide (NO) or reactive oxygen intermediates (ROI). Excessive poly-(ADP-ribose) formation by PARP has been assumed to deplete cellular NAD+ pools and to induce the death of several cell types, including the loss of insulin-producing islet cells in type I diabetes. In the present study we used cells from mice with a disrupted and thus inactivated PARP gene to provide direct evidence for a causal relationship between PARP activation, NAD+ depletion, and cell death. We found that mutant islet cells do not show NAD+ depletion after exposure to DNA-damaging radicals and are more resistant to the toxicity of both NO and ROI. These findings directly prove that PARP activation is responsible for most of the loss of NAD+ following such treatment. The ADP-ribosylation inhibitor 3-aminobenzamide partially protected islet cells with intact PARP gene but not mutant cells from lysis following either NO or ROI treatment. Hence the protective action of 3-aminobenzamide must be due to inhibition of PARP and does not result from its other pharmacological properties such as oxygen radical scavenging. Finally, the use of mutant cells an alternative pathway of cell death was discovered which does not require PARP activation and NAD+ depletion. In conclusion, the data prove the causal relationship of PARP activation and subsequent islet cell death and demonstrate the existence of an alternative pathway of cell death independent of PARP activation and NAD+ depletion.
...
PMID:Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. 774 49

Despite extensive studies on streptozotocin, alloxan and nitric oxide toxicity in pancreatic islets the mechanism of oxygen radical induced islet cell death has not been determined. The present study shows at the level of single cells that following exposure to oxygen radicals generated from xanthine oxidase DNA strand breaks occur in cell nuclei within 5-60 min and precede cell death by several hours. Similar kinetics were seen when treating islet cells with the alkylating agent streptozotocin. Immunofluorescence studies demonstrated the endogenous formation of ADP-ribose polymers in nearly all islet cell nuclei within minutes of treatment with xanthine oxidase, indicating activation of the enzyme poly(ADP-ribose) polymerase (PARP). Concomitantly, cellular NAD+ depletion was noted. Nicotinamide largely prevented NAD+ depletion and in parallel resulted in islet cell survival. These findings identify islet cell nuclear DNA as a primary target of oxygen radical toxicity and suggest related pathways of oxygen radical, nitric oxide and streptozotocin toxicity.
...
PMID:Analysis of oxygen radical toxicity in pancreatic islets at the single cell level. 784 Sep 1

Nitric oxide (NO) has been suggested to act as a regulator of endogenous intracellular ADP-ribosylation, based on radiolabelling of proteins in tissue homogenates incubated with [32P]NAD and NO. After the NO-stimulated modification was replicated in a defined system containing only the purified acceptor protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the hypothesis of NO-stimulation of an endogenous ADP-ribosyltransferase became moot. The NO-stimulated, NAD-dependent modification of GAPDH was recently characterized as covalent binding of the whole NAD molecule to the enzyme, not ADP-ribosylation. With this result, along with the knowledge that GAPDH is stoichiometrically S-nitrosylated, the role of NO in protein modification with NAD may be viewed as the conferring of an unexpected chemical reactivity upon GAPDH, possibly due to nitrosylation of a cysteine in the enzyme active site.
...
PMID:Nitric oxide and NAD-dependent protein modification. 789 64

Recent studies of long-term potentiation (LTP) in the CA1 region of the hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generated NO is a candidate to act as a retrograde messenger. However, the molecular target(s) of NO in LTP remain to be elucidated. The present study examined whether either of two potential NO targets, a soluble guanylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC 2.4.2.31) plays a role in LTP. The application of membrane-permeant analogs of cGMP did not produce any long-lasting alterations in synaptic strength. In addition, application of a cGMP-dependent protein kinase inhibitor did not prevent LTP. 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. The extracellular application of these same inhibitors prevented LTP. Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylation plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action.
...
PMID:An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. 799 64

Previous studies in our laboratory have shown that nitric oxide (NO) gas enhances NMDA-stimulated release of preloaded tritiated norepinephrine ([3H]NA) from rat brain slices in a dose-dependent, oxygen-sensitive, and cyclic GMP-independent manner. In this study we have attempted to determine the mechanism for the enhancement of neurotransmitter release seen with NO. No-enhanced transmitter release was not due to buffer acidification or generation of NO degradation products, since reducing buffer pH below 7.3 inhibited NMDA-stimulated [3H]NA release and nitrite or nitrate ions (3-100 microM) had no significant effect on release. Carbon monoxide (CO, 10-300 microM), another diatomic gas with properties similar to NO including heme binding and guanylate cyclase activation, had no significant effect on depolarization-induced [3H]NA release. The NO effect was probably not due to mono-ADP-ribosylation of cellular proteins, since the ADP-ribosyltransferase (ADPRT) inhibitors nicotinamide (10 microM-10 microM) and luminol (1 microM-1mM) did not diminish the enhancement of transmitter release seen with NO. The NA reuptake inhibitor desmethylimipramine (DMI, 10 nM-10 microM) neither mimicked nor blocked the effect of NO, suggesting that NO was not acting via inhibition or reversal of the NA transporter. Similar to NO, the metabolic inhibitors sodium azide (NaN3, 0.1-3 mM), potassium cyanide (KCN, 0.1-3 mM), and 2,4-dinitrophenol (2,4-DNP, 10-300 microM) also dose-dependently enhanced NMDA-stimulated [3H]NA release. These results suggest that NO may enhance neurotransmitter release by inhibiting cellular respiration and perhaps ultimately via altering calcium homeostasis.
...
PMID:Mechanism for nitric oxide's enhancement of NMDA-stimulated [3H]norepinephrine release from rat hippocampal slices. 853 39


1 2 3 4 5 6 7 8 9 10 Next >>

---