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:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of primary cultures of embryonic rat striatal neurons to agents releasing nitric oxide (NO), including sin-1 molsidomine, S-nitroso-n-acetyl-penicillamine (SNAP), and S-nitrosoglutathione, resulted in an increase in the levels of expression of the immediate early genes c-fos and zif/268 in the cultured neurons. The membrane-permeable cGMP analogue, 8-bromo-cGMP, did not significantly affect c-fos and zif/268 mRNA levels, and the highly selective inhibitor of cGMP-dependent protein kinase, KT5823, was unable to inhibit the elevation in c-fos and zif/268 mRNA levels induced by SNAP. The induction of c-fos by the calcium ionophore A23187 was reduced by treatment with SNAP or 8-bromo-cGMP. Inhibitors of ADP-ribosyltransferases attenuated the stimulation of c-fos expression by SNAP. These results demonstrate for the first time that NO can induce immediate early gene expression in neurons, suggesting that NO may act as a mediator of neuronal plasticity via alterations in the expression of downstream genes. In addition, the results suggest that NO may exert these effects through a pathway that does not involve guanylate cyclase and cGMP-dependent protein kinase.
...
PMID:Stimulation of immediate early gene expression in striatal neurons by nitric oxide. 755 90

Nitric oxide (NO) increases cytosolic guanylate cyclase activity and thereby activates the cGMP signal transduction pathway. The cAMP and Ca2+/phospholipid signal transduction pathways activate transcription factors that bind to the cAMP response element (CRE) and phorbol ester response element (TRE), respectively. Little is known about transcriptional regulation of gene expression by NO/cGMP. In transient and stable transfection experiments and in microinjection studies we found that three different NO-releasing agents and two membrane-permeable cGMP analogs activated TRE-regulated but not CRE-regulated reporter genes in rodent fibroblast and epithelial cell lines. Activation of TRE-regulated genes by NO-releasing agents and cGMP analogs appeared to be mediated by the AP-1 (Jun/Fos) transcription factor complex because we observed increased DNA binding of AP-1 and increased junB and c-fos mRNA in cells treated with these agents. The mechanism of gene activation by NO/cGMP was distinct from that used by phorbol esters and cAMP because it was not associated with c-jun mRNA induction and was not observed with CRE-containing promoters.
...
PMID:Nitric oxide and cGMP analogs activate transcription from AP-1-responsive promoters in mammalian cells. 773 65

Sodium nitroprusside and sodium nitrite, which generate nitric oxide and increase the intracellular cGMP concentration, and 8-bromo-cGMP, a membrane-permeable cGMP analog, induce myelomonocytic differentiation of HL-60 cells (Boss, G. R. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7174-7178). We have selected HL-60 cells resistant to nitroprusside-induced differentiation as assessed by acquisition of the OKM-1 antigen, reduction of nitro blue tetrazolium, and morphologic maturation. The variant cells were also resistant to differentiation induced by sodium nitrite and two cGMP analogs but still differentiated in response to other inducing agents such as dimethyl sulfoxide and cAMP analogs and showed the same changes in c-myc and c-fos expression in response to the latter drugs as occurred in parental cells. We studied the early steps of the NO/cGMP signal transduction pathway in the variant cells and found that basal and nitroprusside-stimulated guanylate cyclase activity was similar in parental and variant cell extracts and that nitroprusside increased the intracellular cGMP concentration to the same extent in parental and variant cells. As part of these studies we found that HL-60 cells expressed only alpha 2 and beta 2 guanylate cyclase mRNA; the abundance of these two mRNA species was similar in parental and variant cells. Neither nitroprusside nor 8-bromo-cGMP changed the intracellular calcium concentration in parental or variant cells. The data suggest that the defect in the variant cells is after guanylate cyclase activation in the NO/cGMP transduction pathway and that the cGMP and cAMP transduction pathways operate independently in inducing differentiation of HL-60 cells.
...
PMID:Isolation and characterization of HL-60 cells resistant to nitroprusside-induced differentiation. 779 12

Stimulation of several second messenger pathways induces the expression of immediate early genes such as c-fos, c-jun, junB, and junD, but little is known about their induction via the stimulation of the cyclic GMP pathway. Here we looked at the expression of early genes in pheochromocytoma PC12 cells after activation of cytosolic guanylate cyclase by sodium nitroprusside. This compound spontaneously releases NO, a molecule known to be involved in cell communication. We found that expression of c-fos and junB but not of c-jun or junD is increased upon activation of cyclic GMP pathway. c-fos mRNA expression was the most activated (fourfold at 30 min), whereas junB response was more modest (2.2-fold activation at 60 min). Nuclear extracts of stimulated cells show increased binding capacity to the AP1 binding site consistent with the dose-response curve. The activating effect of nitroprusside could be reproduced by dipyridamole, a selective cyclic GMP phosphodiesterase inhibitor and by 8-p-chlorophenylthio-cyclic GMP, a permeant selective cyclic GMP-dependent protein kinase activator, and abolished by KT5823, an inhibitor of that kinase. The results show that NO promotes early gene activation and AP1 binding enhancement through the stimulation of the cyclic GMP pathway.
...
PMID:Stimulation of the cyclic GMP pathway by NO induces expression of the immediate early genes c-fos and junB in PC12 cells. 829 11

Previous studies have shown that exposure of Swiss 3T3 cells to mainstream cigarette smoke (CS) trapped in phosphate-buffered saline (smoke-bubbled PBS) resulted in the expression of stress response genes, i.e. haem oxygenase and c-fos, partial inhibition of protein phosphatases 1 and 2A, as well as partial depletion of the cellular glutathione (GSH) pool. Using c-fos gene expression in Swiss 3T3 cells as an indicator for a cellular response against oxidative stress, the following observations are consistent with peroxynitrite as an active principal formed by CS in aqueous solutions: (i) sustained c-fos expression was obtained for smoke-bubbled PBS, peroxynitrite itself and a compound known to stoichiometrically release superoxide and nitric oxide (NO) (3-morpholino-sydnonimine, SIN-1); (ii) c-fos expression in cells exposed to aqueous smoke fractions was inhibited by either the superoxide-scavenging enzyme superoxide dismutase (SOD), in combination with catalase, or the NO-scavenger oxyhaemoglobin (HbO2); and (iii) activation of guanylate cyclase in rat lung cells was observed only when bubbling was performed with filtered smoke and with whole smoke in the presence of SOD/catalase. These results are consistent with a rapid NO-consuming reaction coupled with superoxide-generating properties of the particulate phase of CS. Moreover, (iv) the half-life of the c-fos-inducing activity in smoke-bubbled PBS was found to be <1 h which can be explained by a sustained peroxynitrite formation. Finally, depletion of intracellular thiol levels by smoke-bubbled PBS appears to favour the activation of a redox-sensitive component of the c-fos-inducing pathway.
...
PMID:Evidence for peroxynitrite as an oxidative stress-inducing compound of aqueous cigarette smoke fractions. 905 21

Recognition of the role of nitric oxide in cell-to-cell communication has changed the concept of traditional neurotransmission. We have shown previously that N-methyl-D-aspartate receptors mediate dipsogenic responses and c-Fos expression induced by intracerebroventricular infusion of angiotensin II. Since these receptors are known to be linked to the nitric oxide-cyclic GMP pathway, the present study explores the contribution of this path to the behavioural and cellular effects of intracerebroventricular angiotensin II by using behavioural testing, NADPH-diaphorase histochemistry and immunocytochemical staining for the immediate-early gene, c-fos. N(G)-nitro-L-arginine methyl ester (125 and 250 microg, intracerebroventricular), an inhibitor of nitric oxide synthase, and Methylene Blue (100 microg), an inhibitor of guanylate cyclase activation, antagonized water intake induced by intracerebroventricular injection of 25 pmol angiotensin II. The effects of N(G)-nitro-L-arginine methyl ester were reversed by co-injection of L-arginine, the substrate for nitric oxide synthase. However, N(G)-nitro-L-arginine methyl ester did not alter the pattern of angiotensin II-induced c-fos expression in the organum vasculosum of the lamina terminalis, median preoptic nucleus, hypothalamic paraventricular nucleus and supraoptic nucleus. Double staining with NADPH-diaphorase histochemistry and c-Fos immunocytochemistry showed that neurons staining for both were localized to the anterior third ventricle. However, only 19-25% of the c-Fos-positive neurons expressed NADPH. There were also substantial numbers of neurons in which angiotensin II induced c-Fos that were NADPH-negative. Extensive co-distribution of NADPH-diaphorase-stained cells and those expressing c-fos in response to intracerebroventricular injection of angiotensin II, especially in the median preoptic nucleus, imply that nitric oxide might participate in the mechanism of angiotensin II-induced drinking behaviour. However, a low rate of co-localization of the two markers to individual cells suggests that angiotensin II stimulated the production of nitric oxide and c-Fos in different populations of neurons. Since our previous results showed that glutamate blockade, but not nitric oxide synthase inhibition, suppressed angiotensin II-induced c-Fos, the experiments reported here further suggest that nitric oxide release is not an essential requirement for the expression of c-fos elicited by angiotensin II. They also provide evidence that the dipsogenic and c-Fos responses to angiotensin II are dissociated at a cellular level.
...
PMID:Angiotensin II interacts with nitric oxide-cyclic GMP pathway in the central control of drinking behaviour: mapping with c-fos and NADPH-diaphorase. 920 Jul 37

Several lines of evidence have shown a role for the nitric oxide/cyclic guanosine monophosphate signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cyclic guanosine monophosphate are not fully understood in the processing of pain in the spinal cord. The present study showed that cyclic guanosine monophosphate-dependent protein kinase Ialpha but not Ibeta was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of a selective inhibitor of cyclic guanosine monophosphate-dependent protein kinase Ialpha, Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine, produced a significant antinociception demonstrated by the decrease in the number of flinches and shakes in the formalin test. This was accompanied by a marked reduction in formalin-induced c-fos expression in the spinal dorsal horn. Moreover, cyclic guanosine monophosphate-dependent protein kinase Ialpha protein expression was dramatically increased in the lumbar spinal cord 96 h after injection of formalin into a hindpaw, which occurred mainly in the superficial laminae on the ipsilateral side of a formalin-injected hindpaw. This up-regulation of cyclic guanosine monophosphate-dependent protein kinase Ialpha expression was completely blocked not only by a neuronal nitric oxide synthase inhibitor, 7-nitroindazole, and a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, but also by an N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (MK-801). The present results indicate that noxious stimulation not only initially activates but also later up-regulates cyclic guanosine monophosphate-dependent protein kinase Ialpha expression in the superficial laminae via an N-methyl-D-aspartate-nitric oxide-cyclic guanosine monophosphate signaling pathway, suggesting that cyclic guanosine monophosphate-dependent protein kinase Ialpha may play an important role in the central mechanism of formalin-induced inflammatory hyperalgesia in the spinal cord.
...
PMID:Expression and action of cyclic GMP-dependent protein kinase Ialpha in inflammatory hyperalgesia in rat spinal cord. 1065 33

It has been reported that neurovascular compression of the rostral ventrolateral medulla might be causally related to essential hypertension. Recently, we found that pulsatile compression of the rostral ventrolateral medulla increases sympathetic nerve activity and elevates arterial pressure via activation of glutamate receptors in rats. We also found that increases in sympathetic and cardiovascular activities by microinjection of L-glutamate into the rostral ventrolateral medulla are mediated by c-fos expression-related substance(s) following activation of the nitric oxide-cyclic GMP pathway. Herein, we investigated whether responses to pulsatile compression are mediated by local activation of the nitric oxide-cyclic GMP pathway and/or c-fos expression-related substance(s) in rats. Increases in arterial pressure (15+/-1 mmHg), heart rate (9+/-1 b.p.m.), and sympathetic nerve activity (% change: 8.5+/-1.1%) induced by pulsatile compression were partially but significantly inhibited after local microinjection of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (8+/-2 mmHg, 1+/-1 b.p.m., 4.0+/-1.3%; P<0.05 vs compression without pretreatment) or 7-nitroindazole (7+/-2 mmHg, 2+/-1 b.p.m., 4.0+/-1. 5%; P<0.05), or a soluble guanylate cyclase inhibitor, methylene blue (9+/-1 mmHg, 4+/-1 b.p.m., 4.1+/-1.4%; P<0.05). In addition, increases in arterial pressure, heart rate, and sympathetic nerve activity by pulsatile compression were significantly reduced 6 h after microinjection of antisense oligodeoxynucleotide to c-fos mRNA (2+/-2 mmHg, 2+/-1 b.p.m., 1.0+/-1.0%; P<0.05 vs sense oligodeoxynucleotide). These results suggest that increases in sympathetic and cardiovascular activities induced by pulsatile compression of the rostral ventrolateral medulla are mediated, at least in part, by local activation of the nitric oxide-cyclic GMP pathway and c-fos expression-related substance(s) in rats.
...
PMID:Pressor response to pulsatile compression of the rostral ventrolateral medulla mediated by nitric oxide and c-fos expression. 1069 82

The atrial natriuretic peptide (ANP) is suggested to regulate inflammatory response by alteration of macrophage functions. The aim of this study was to investigate whether ANP influences production of TNF-alpha. TNF-alpha production in murine bone marrow-derived macrophages was induced by LPS, and TNF-alpha secretion (+/-ANP) was determined by L929 bioassay. ANP dose dependently (10-8-10-6 M) inhibited TNF-alpha release by up to 95%. The effect was mediated via the guanylate cyclase-coupled A receptor, as was shown by employing dibutyryl-cGMP, the cGMP-inhibitory compound Ly-83583, and the A receptor antagonist HS-142-1. A specific ligand of the natriuretic peptide "clearance" receptor inhibited TNF-alpha production only at 10-7 and 10-8 M, but not at 10-6 M. The B receptor ligand C-type natriuretic peptide showed no TNF-alpha-inhibitory effect. To investigate the underlying mechanism of ANP-mediated TNF-alpha inhibition, Northern blot was performed. ANP-treated macrophages displayed decreased TNF-alpha-mRNA levels. Besides the known inhibition of NF-kappaB activation, in this study we demonstrated that ANP also attenuates the activation of the proinflammatory transcription factor AP-1 (gel shift assay). ANP did not alter subunit composition of AP-1 complexes, as was shown by supershift assays applying anti-c-jun and anti-c-fos Abs. To get information on the ANP effect for human inflammatory processes, we investigated cytokine production in human LPS-activated blood. ANP significantly attenuated production of TNF-alpha and IL-1beta without affecting production of IL-10 and IL-1ra. In summary, ANP was shown to attenuate TNF-alpha production of LPS-activated macrophages via cGMP. The inhibition is suggested to involve transcriptional processes that are the result of reduced activation of responsible transcription factors.
...
PMID:cGMP-mediated inhibition of TNF-alpha production by the atrial natriuretic peptide in murine macrophages. 1086 Oct 50

We have shown that nitric oxide (NO) regulates c-fos gene expression via cGMP-dependent protein kinase (G-kinase), but NO's precise mechanism of action is unclear. We now demonstrate that: (1) NO targets two transcriptional elements in the fos promoter, i.e., the fos AP-1 binding site and the cAMP-response element (CRE); (2) NO activation of these two enhancer elements requires the CRE binding protein CREB because a dominant negative CREB fully inhibits NO transactivation of reporter genes whereas dominant negative Fos or CCAAT enhancer binding proteins have no effect; (3) CREB is phosphorylated by G-kinase in vitro and its phosphorylation increases in vivo when G-kinase is activated either directly by cGMP or indirectly by NO via soluble guanylate cyclase; (4) NO activation of fos promoter elements requires nuclear translocation of G-kinase but not activation of mitogen-activated protein kinases.
...
PMID:NO activation of fos promoter elements requires nuclear translocation of G-kinase I and CREB phosphorylation but is independent of MAP kinase activation. 1117 47


1 2 Next >>

---