Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium nitroprusside (SNP), a widely used nitric oxide donor, has recently been shown to mediate chondrocyte apoptosis by generating reactive oxygen species, whereas more potent nitric oxide donors do not induce chondrocyte apoptosis. The present study was performed to investigate the protective effect of a low concentration of SNP upon the cytotoxicity of chondrocytes to higher concentrations of SNP, and to elucidate the underlying mechanism. Human osteoarthritis chondrocytes were cultured as monolayers, and first-passage cells were used for the experiments. Chondrocyte death induced by 1 mM SNP was completely inhibited by pretreating with 0.1 mM SNP. This protective effect of SNP was replicated by the guanosine-3',5'kappa-cyclic monophosphate analog, DBcGMP. Protection from chondrocyte death conferred by 0.1 mM SNP was mediated by heme oxygenase 1 (HO-1), as was revealed by the increased expression of HO-1 in 0.1 mM SNP pretreated chondrocytes and by the reversal of this protective effect by the HO-1 inhibitor, zinc protoporphyrin. SNP-mediated chondrocyte protection correlated with the downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 kinase activation. SNP at 0.1 mM induced significant NF-kappaB activation as revealed by electrophoretic mobility shift assays, and the inhibition of NF-kappaB by MG132 or Bay 11-7082 nullified 0.1 mM SNP-mediated chondrocyte protection. The upregulation of p53 and the downregulation of Bcl-XL and Mcl-1 by 1 mM SNP were reversed by 0.1 mM SNP pretreatment at the protein level by western blotting. Our study shows that priming with 0.1 mM SNP confers complete protection against cell death induced by 1 mM SNP in human articular chondrocytes. This protective effect was found to be correlated with the upregulation of both HO-1 and NF-kappaB and with the concomitant downregulation of both extracellular signal-regulated protein kinase 1/2 and p38 activation.
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PMID:The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death. 1589 39

Sodium nitroprusside (SNP) is a water-soluble iron nitrosyl complex clinically used as a powerful vasodilator for treatment of hypertension; and, in basic research, it has been used to mainly investigate the cytotoxic effects of nitrosative stress. Although NO is considered a pharmacologically active molecule, not all of the biological effects of SNP are dependent on its NO moiety. To elucidate the molecular executioner(s) responsible for SNP cytotoxicity, this study determines the involvement of oxidative stress in p53 activation and apoptotic induction elicited by SNP in SH-SY5Y neuroblastoma cells. We demonstrate that proapoptotic activity of SNP is independent of NO production, because SNP and its 2-day light-exhausted compound SNP(ex) trigger apoptosis to the same extent. We provide evidence for the occurrence of oxidative stress and oxidative damage during both SNP and SNP(ex) exposure and demonstrate that iron-derived reactive oxygen species (ROS) are the genuine mediators of their cytotoxicity. We show that p53 is equally activated upon both SNP and SNP(ex) treatments. Moreover, as demonstrated by small interfering RNA experiments, we indicate its primary role in the induction of apoptosis, suggesting the ineffectiveness of NO in its engagement. The attenuation of p53 levels, obtained by oxy-radical scavengers, is consistent with the recovery of cell viability and ROS decrease, demonstrate that SNP-mediated p53 activation is an event triggered by ROS and/or ROS-mediated damages. Together, our results suggest that investigations of the physiopathological effects of SNP should consider the role of ROS, other than NO, particularly in some conditions such as apoptotic induction and p53 activation.
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PMID:Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. 1867 76

Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.
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PMID:Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein. 2249 83