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)

Increases in plasma cyclic GMP levels have been shown to correlate with increased plasma levels of atrial natriuretic peptide (ANP) in patients with fluid overload due to increased secretion of ANP. There is evidence that plasma cyclic GMP levels are also elevated in some patients with acute leukemia, but increased ANP secretion has not been demonstrated. To elucidate the possibility that a newly expressed guanylyl cyclase may be responsible for the increase of plasma cyclic GMP levels patients with acute and chronic leukemia as well as patients with lymphoma and healthy volunteers were studied. Plasma levels of cyclic GMP were measured and isolated peripheral blood mononuclear or bone marrow cells were incubated with increasing concentrations of ANP. The stimulation of cells was measured as cGMP accumulation in the supernatant. Furthermore guanylyl cyclase activity was measured in membrane preparations of peripheral blood mononuclear cells. While leukocytes of healthy subjects were devoid of detectable ANP-stimulated particulate guanylyl cyclase activity, ANP-sensitivity was observed in seven patients with acute lymphoblastic and in three patients with acute myelogenous leukemia. Cyclic GMP in the supernatant of cells was elevated between 2- and 132-fold of basal when cells were incubated with 1 microM ANP for 60 minutes. Like in healthy volunteers, no effect of ANP on freshly isolated mononuclear cells was observed in cases with chronic leukemia or in patients with lymphoma. Expression of ANP-sensitive particulate gunaylyl cyclase may be connected with malignant transformation of lymphocytes in patients with acute leukemia and might be useful for their diagnosis and classification.
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PMID:Particulate ANP-sensitive guanylyl cyclase in blood and bone marrow cells of patients with acute leukemia. 911 98

We have determined the complete genomic nucleotide sequence and analyzed the promoter region of murine guanylyl cyclase/natriuretic peptide receptor-A gene (Npr1,coding for NPRA). The gene spans about 17.8 kb and contains 22 exons interrupted by 21 introns. All the exon-intron boundaries possess the consensus GT/AG splice junctions. Four different types of short interspersed nuclear elements (ten mouse B1 elements, seven mouse B2-B4 elements, one ID and one MIR element) and one medium reiteration frequency repeats have been found in the non-coding regions of the gene. Eleven tandem repeats, including three in the promoter region of the gene, have been identified. The transcription start site, 362 bp upstream from the start codon, was determined by 5'- rapid amplification of cDNA ends. The 1.98 kb 5'-flanking region contains three potential SP1 binding sites and one inverted CCAAT box but lacks the TATA box. This region also contains several putative cis-acting motifs known to bind kidney specific nuclear protein HFH-3, cAMP-responsive element binding protein (CREB) and AP-4. In addition, the binding sites for a variety of transcription factors: AML-1 alpha, SRY, Nkx-2.5, LyF-1, p300, GATA-1/2, HNF-3 beta, c/EBP alpha/beta and USF have been localized in the promoter region of Npr1 gene. The analyses and characterization of the genomic structure of murine Npr1 gene should yield important insights into the species-specific regulation of this important gene family.
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PMID:Genomic structure, organization, and promoter region analysis of murine guanylyl cyclase/atrial natriuretic peptide receptor-A gene. 1209 86