Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Activation of a cytosolic ADP-ribosyltransferase by nitric oxide-generating agents. 254 78

Sodium nitroprusside (SNP)-treated PC12 cell line is being used in our laboratory as a cell model of nitric oxide (NO)-mediated damage for in vitro evaluation of potential neuroprotective compounds, thus cell response to SNP must be standardized to gain reproducible data. The NO-donor SNP has been shown to induce cell death at high concentrations in undifferentiated PC12 cells. Differences were found in sensitivity to SNP between cells from short- and long-term cultured cells. After 24-h exposure to 100-500 microM SNP, a decrease of cell viability was observed in both short- (17, 21 and 23rd passages) and long-term cultures (46, 49 and 50th passages), with IC(50) values of 312.72 and 462.90 microM, respectively. In cells from early passages, SNP-induced cell death was accompanied by significant increases of LDH leakage, nitrite production, malondialdehyde (MDA) levels, catalase (CAT) activity, cleavage of poly(ADP-ribose)polymerase (PARP) and caspase-3 activation in comparison with those from late passages. Furthermore, untreated and SNP-treated cells from long-term cultures displayed an increase of the stress protein Hsp70 levels when compared with those from short-term cultures. Up-regulated levels of Hsp70 may be associated with cell survival. Therefore, cells may acquire a certain resistance to SNP-induced toxicity associated with an increase in cell passage-dependent Hsp70. The protein Hsp70 might modulate the cellular response to the toxic insult by increasing CAT and GSH-Px activities and decreasing caspase-3 activation. Finally, it is crucial for the standardization of this cell model of neurotoxicity, at least in part, the use of PC12 cells in an optimum and reliable range of passages.
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PMID:Involvement of Hsp70, a stress protein, in the resistance of long-term culture of PC12 cells against sodium nitroprusside (SNP)-induced cell death. 2055 25