Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultraviolet A (UVA) irradiated human squamous cell carcinoma (SCC-13) releases nitrogen oxides, i.e. nitric oxide (NO), peroxynitrite (ONOO-), nitrosocompounds, ammonia (NH3) and hydroxylamine (H2NOH) formed from L-arginine. Formation and/or release of these nitrogen oxides was time and concentration-dependently stimulated by UVA and decreased by N-monomethyl-L-arginine (L-NMMA), a compound that inhibits NO synthase activity. UVA irradiation of SCC-13 cells resulted in concomitant increase in soluble guanylate cyclase (sGC) which was inhibited by L-NMMA. The increased NO and ONOO- production evoked by dibutyryl cGMP and 3-isobutyl-l-methyl-xanthine (IBMX) represents an additional positive feedback mechanism that could serve to maintain NO and ONOO- release for extended periods following UVA radiation. Using an in vitro chemical model system, it was demonstrated that oxidation of NH3 to NO by hydroxyl radical (.OH) at physiological pH is chemically feasible. UVA irradiated SCC-13 cells induced a luminol-enhanced chemiluminescence signal that reaches a peak within 1 min. The modulation of this signal by ebselen is consistent with a rate-determining step corresponding to the disproportionation of a luminol-superoxide (O2-) complex. UVA irradiated SCC-13 cells promptly increased malondialdehyde (MDA) production with subsequent decrease of plasma membrane fluidity. Desferrioxamine tested in UVA irradiated SCC-13 cells showed a concentration dependent decrease in MDA production with subsequent restoration of the membrane fluidity to the normal level. Furthermore, it was shown that squamous cell carcinoma possesses higher NO synthase and sGC activity as compared to normal keratinocytes. Such an increase in NO production may be directly related to the poor prognosis of squamous cell carcinoma.
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PMID:Nitric oxide, peroxynitrite and nitroso-compounds formation by ultraviolet A (UVA) irradiated human squamous cell carcinoma: potential role of nitric oxide in cancer prognosis. 754 92

In the present study we demonstrated that synaptosomes isolated from rabbit brain cortex contain NO synthase and xanthine oxidase that can be activated by ultraviolet B radiation and Ca2+ accumulation to produce nitric oxide and superoxide which react together to form peroxynitrite. Irradiation of synaptosomes with ultraviolet B (up to 100 mJ/cm2), or increase the intrasynaptosomal calcium concentration using various doses (up to 100 mu M) of the calcium ionophore A 23187, a gradual increase in both nitric oxide and peroxynitrite release that was inhibited by N-monomethyl-L-arginine (100 mu M) was observed. The rate of nitric oxide release and cyclic GMP production by NO synthase and soluble guanylate cyclase, both located in the soluble fraction of synaptosomes (synaptosol), were increased approximately eight fold after treatment of synaptosomes with Ultraviolet B radiation (100 mJ/cm2). In reconstitution experiments, when purified NO synthase isolated from synaptosol was added to xanthine oxidase, in the presence of the appropriate cofactors and substrates, a ten fold increase in peroxynitrite production at various doses (up to 20 mJ/cm2) of UVB radiation was observed. Ultraviolet B irradiated synaptosomes promptly increased malondialdehyde production with subsequent decrease of synaptosomal plasma membrane fluidity estimated by fluorescence anisotropy of 1-4-(trimethyl-amino-phenyl)-6-phenyl-hexa-1 ,3,5-triene. Desferrioxamine (100 mu M) tested in Ultraviolet B-irradiated synaptosomes showed a decrease (approximately 80%) in malondialdehyde production with subsequent restoration of the membrane fluidity to that of non-irradiated (control) synaptosomes. Ca(2+)-stimulated ATPase activity was decreased after Ultraviolet B (100 mJ/cm2) radiation of synaptosomes indicating that the subsequent increase of intrasynaptosomal calcium promoted peroxynitrite production by a calmodulin-dependent increase of NO synthase and xanthine oxidase activities. Furthermore, it was shown that UVB-irradiated synaptosomes were subjected to higher oxidative stress by exogenous peroxynitrite (100 mu M) compared to non-irradiated (control) synaptosomes. In summary, the present results indicate that activation of NO synthase and xanthine oxidase of brain cells lead to the formation of peroxynitrite providing important clues in the role of peroxynitrite as a causative factor in neurotoxicity.
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PMID:NO synthase and xanthine oxidase activities of rabbit brain synaptosomes: peroxynitrite formation as a causative factor of neurotoxicity. 883 24

Nitric oxide (NO) is a potent inducer of heme oxygenase (HO)-1, and NO-induced HO-1 expression is dependent on the cGMP-signaling pathway. Sodium nitroprusside (SNP) produces NO and iron. However, it is unclear whether NO is exclusively responsible for induction of HO-1 by SNP in RAW 264.7 cells. We tested our hypothesis that iron may contribute more to the SNP induction of HO-1 than does NO by comparing the HO-1 protein level and the production of NO in RAW 264.7 cells treated with SNP and S-nitroso-N-acetyl-DL-penicillamine (SNAP). Although SNP induced less NO production than SNAP, SNP induced the production of more HO-1 protein than did SNAP. Deferoxamine (DFO) decreased SNP- but not SNAP-induced HO-1 expression but did not decrease the production of NO. SNP-induced HO-1 was significantly inhibited by specific protein kinase A (PKA) inhibitors or an antagonist of cAMP but not by guanylyl cyclase inhibitors. Exogenous iron (ferric ammonium citrate or ferricyanide) and forskolin increased the level of HO-1, which was inhibited by PKA inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89). These results indicate that iron and cAMP, but not cGMP, play crucial roles in the induction of HO-1 in RAW 264.7 cells. Moreover, DFO and inhibitors of extracellular signal-related kinases 1/2 or c-Jun NH(2)-terminal kinase inhibited HO-1 production induced by SNP. This study illustrates that iron rather than NO from SNP contributes to HO-1 induction. Therefore, studies on the effects of SNP should consider the role of iron in some biological functions. We concluded that iron released by SNP contributes to HO-1 induction via the cAMP-PKA-mitogen-activated protein kinase pathway.
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PMID:Iron released by sodium nitroprusside contributes to heme oxygenase-1 induction via the cAMP-protein kinase A-mitogen-activated protein kinase pathway in RAW 264.7 cells. 1647 85