Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane-bound pool of calcium stores, and Quin-2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LJP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils. 839 75

Plasma membranes from liver of control rats or from chemical-induced hepatoma were prepared. The basal activity of adenylate cyclase was increased significantly in the rat plasma membranes of DEN-induced hepatoma compared to normal tissue. The glucagon-induced response on the cellular effector systems via guanine nucleotide-binding regulatory proteins (G proteins) was inhibited in hepatoma plasma membranes. These findings suggest that in hepatoma membranes, unlike normal hepatic membranes, the response to hormonal stimuli through regulatory G proteins results in a loss of response to glucagon, as well as to GTP plus glucagon or to GTP gamma S. However, the activating effects of forskolin, which catalyses the formation of cyclic AMP from ATP acting on the catalytic subunit, were to some extent retained. The methyltransferase-I behaved in the opposite direction to the adenylate cyclase, showing a decreased activity in hepatoma plasma membranes compared to control membranes. In contrast, the activity of the ecto-5'-nucleotidase was significantly increased in hepatoma. These enzymatic changes have been found to influence the membrane fluidity and to be responsible for the ultrastructural modifications of hepatoma plasma membranes which are induced by chemical carcinogens.
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PMID:Enzymatic, biophysical and ultrastructural changes of plasma membranes in chemical-induced rat hepatoma. 856 46

Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. In the chicken pineal gland, HIOMT mRNA concentration exhibits a circadian rhythm with a threefold peak at midday. The present study sought to evaluate the possible role of cyclic AMP in this transcriptional rhythm. In cultured pineal glands from 4-day-old chicks, cyclic AMP analogs and the adenylate cyclase activator, forskolin, increased HIOMT mRNA levels twofold to threefold in a dose-dependent manner. Vasoactive intestinal polypeptide increased HIOMT mRNA levels by 50%. Actinomycin-D chase experiments indicated that cyclic AMP did not affect the stability of HIOMT mRNA, thus providing indirect evidence that the effect of cyclic AMP was exerted at transcriptional level. In cultured pineal glands from 11 days embryos, HIOMT mRNA levels failed to respond to cyclic AMP. However, a daily rhythm of HIOMT mRNA, with an endogenous component in constant darkness was clearly observed at this developmental stage. This observation indicates that cyclic AMP is not required for circadian rhythmicity of HIOMT gene transcription.
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PMID:Cyclic AMP increases hydroxyindole-O-methyltransferase mRNA levels in the chicken pineal gland, but is not required for circadian rhythmicity of this transcript. 1041 64

Anatomical and functional studies of the autonomic innervation of the photophores of luminescent fishes are scarce. The present immunohistochemical study demonstrated the presence of nerve fibers in the luminous epithelium and lens epithelium of the photophores of the hatchet fish, Argyropelecus hemigymnus and identified the immunoreactive elements of this innervation. Phenylethanolanine N-methyltransferase (PNMT) and catecholamine (CA)-synthesizing enzymes were detected in nerve varicosities inside the two epithelia. Neuropeptides were localized in neuropeptide Y (NPY) and substance P (SP)- and its NK11 receptor-immunopositive nerves in the lens epithelium. Neuropeptides were also localized in non-neural cell types such as the lens cells, which displayed immunoreactivities for pituitary adenylate cyclase activating peptide (PACAP) and their receptors R-12 and 93093-3. This reflects the ability of the neuropeptide-containing nerves and lens cells to turn on and off the expression of selected messengers. It appears that the neuropeptide-containing nerves demonstrated in this study may be sensory. Furthermore, neuronal nitric oxide synthase-immunopositive axons associated with photocytes in the luminous epithelium have previously been described in this species. Whereas it is clear that the photophores receive efferent (motor) fibers of spinal sympathetic origin, the origin of the neuropeptide sensory innervation remains to be determined. The functional roles of the above neuropeptides or their effects on the bioluminescence or the chemical nature of the terminals, either sensory or postganglionic neurons innervating the photophores, are still not known.
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PMID:Immunolocalization of neurotransmitter-synthesizing enzymes and neuropeptides with associated receptors in the photophores of the hatchetfish, Argyropelecus hemigymnus Cocco, 1829. 2054 67

The nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'-cAMP) plays important physiological roles, ranging from carbon catabolite repression in bacteria to mediating the action of hormones in higher eukaryotes, including human. However, it remains unclear whether 3',5'-cAMP is universally present in the Firmicutes group of bacteria. We hypothesized that searching for proteins that bind 3',5'-cAMP might provide new insight into this question. Accordingly, we performed a genome-wide screen and identified the essential Staphylococcus aureus tRNA m1G37 methyltransferase enzyme TrmD, which is conserved in all three domains of life as a tight 3',5'-cAMP-binding protein. TrmD enzymes are known to use S-adenosyl-l-methionine (AdoMet) as substrate; we have shown that 3',5'-cAMP binds competitively with AdoMet to the S. aureus TrmD protein, indicating an overlapping binding site. However, the physiological relevance of this discovery remained unclear, as we were unable to identify a functional adenylate cyclase in S. aureus and only detected 2',3'-cAMP but not 3',5'-cAMP in cellular extracts. Interestingly, TrmD proteins from Escherichia coli and Mycobacterium tuberculosis, organisms known to synthesize 3',5'-cAMP, did not bind this signaling nucleotide. Comparative bioinformatics, mutagenesis, and biochemical analyses revealed that the highly conserved Tyr-86 residue in E. coli TrmD is essential to discriminate between 3',5'-cAMP and the native substrate AdoMet. Combined with a phylogenetic analysis, these results suggest that amino acids in the substrate binding pocket of TrmD underwent an adaptive evolution to accommodate the emergence of adenylate cyclases and thus the signaling molecule 3',5'-cAMP. Altogether this further indicates that S. aureus does not produce 3',5'-cAMP, which would otherwise competitively inhibit an essential enzyme.
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PMID:Evolutionary Adaptation of the Essential tRNA Methyltransferase TrmD to the Signaling Molecule 3',5'-cAMP in Bacteria. 2788 78


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