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)

The generation of neurons and glia in the developing nervous system is likely to be regulated by extrinsic factors, including growth factors and neurotransmitters. Evidence from in vivo and/or in vitro systems indicates that basic fibroblast growth factor, transforming growth factor (TGF)-alpha, insulin-like growth factor-1, and the monoamine neurotransmitters act to increase proliferation of neural precursors. Conversely, glutamate, gamma-aminobutyric acid, and opioid peptides are likely to play a role in down-regulating proliferation in the developing nervous system. Several other factors, including the neuropeptides vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide, as well as the growth factors platelet-derived growth factor, ciliary neurotrophic factor, and members of the TGF-beta family, have different effects on proliferation and differentiation depending on the system examined. Expression of many of these factors and their receptors in germinal regions of the central nervous system suggests that they can act directly on precursor populations to control their proliferation. Together, the findings discussed here indicate that proliferation and cell fate determination in the developing brain are regulated extrinsically by complex interactions between a relatively large number of growth factors and neurotransmitters.
 ...
PMID:Regulation of neurogenesis by growth factors and neurotransmitters. 971 10

In a recent communication, we demonstrated that prostaglandin E2 (PGE2) lowers basal while it ablates interleukin-1beta((IL-1beta) and transforming growth factor-beta (TGFbeta) upregulated lysyl oxidase (LO) mRNA levels. Correspondingly, PGE2 increases cyclooxygenase-1 (COX1) mRNA in diploid, human embryo lung fibroblasts (IMR90) [Roy et al., 19961. We now report that these actions by PGE2 are routed through cAMP via the PGE2, EP2 receptor. Among the PGE2 receptor types, the IMR90 predominantly express the EP2 mRNA. These cells also express EP3 and EP4 mRNA at comparatively low levels. Northern blot analyses show that 11-deoxy PGE1, an EP2/EP4 agonist, emulates the action of PGE2. In a similar manner to PGE2, 11-deoxy PGE1 decreases basal and TGF-beta induced type I collagen alpha1 (COL) mRNA, basal and IL-1beta induced LO mRNA while it increases COX1 mRNA. Sulprostone, an EP3/EP1 agonist, has no effect on the expression of these three genes. Forskolin, an adenylate cyclase activator, acts in a very similar manner to PGE2 or 11-deoxy PGE1. It suppresses both basal and TGF-beta induced COL mRNA levels. Both PGE2 and 11-deoxy PGE1 increase cAMP to a level comparable with forskolin. The role of the EP2 receptor in controlling collagen production is further underscored in the immortalized Rat-1 fibroblasts, derived from Fischer rat embryos, which do not express detectable EP2 mRNA. In these cells, PGE2 has little effect on COL mRNA level, whereas forskolin increases it. Furthermore, forskolin increases cAMP level in Rat-1 cells, whereas PGE2 does not. Overall, these results illustrate that much of the PGE2 action on the expression of COL, LO, and COX1 genes is mediated through the EP2 receptor and a subsequent increase in intracellular cAMP.
 ...
PMID:Role of EP2 receptors and cAMP in prostaglandin E2 regulated expression of type I collagen alpha1, lysyl oxidase, and cyclooxygenase-1 genes in human embryo lung fibroblasts. 977 23

Retrograde signaling is an essential component of synaptic development and physiology. Previous studies show that bone morphogenetic protein (BMP)-dependent retrograde signaling is required for the proper development of the neuromuscular junction (NMJ) in Drosophila. These studies, moreover, raised the significant possibility that the development of central motor circuitry might similarly be reliant on such signaling. To test this hypothesis, retrograde signaling between postsynaptic motoneurons and their presynaptic interneurons is examined. Postsynaptic expression of an adenylate cyclase encoded by rutabaga (rut), is sufficient to strengthen synaptic transmission at these identified central synapses. Results are presented to show that the underlying mechanism is dependent on BMP retrograde signaling. Thus, presynaptic expression of an activated TGF-beta receptor, thickvien (tkv), or postsynaptic expression of a TGF-beta ligand, glass-bottom boat (gbb), is sufficient to phenocopy strengthening of synaptic transmission. In the absence of gbb, endogenous synaptic transmission is significantly weakened and, moreover, postsynaptic overexpression of rut is unable to potentiate synaptic function. Potentiation of presynaptic neurotransmitter release, mediated by increased postsynaptic expression of gbb, is dependent on normal cholinergic activity, indicative that either the secretion of this retrograde signal, or its transduction, is activity dependent. Thus, in addition to the development of the NMJ and expression of myoactive FMRFamide-like peptides in specific central neurons, the results of the present study indicate that this retrograde signaling cascade also integrates the development and function of central motor circuitry that controls movement in Drosophila larvae.
 ...
PMID:Synaptic strengthening mediated by bone morphogenetic protein-dependent retrograde signaling in the Drosophila CNS. 1529 25

Both alpha-adrenoceptor- and beta-adrenoceptor-stimulation lead to hypertrophic growth of the myocardium. But only beta-adrenoceptor-stimulation requires the pre-cultivation of cells with active TGF-beta. In order to define signalling molecules that are specifically involved in beta-adrenoceptor-dependent hypertrophy, changes in expression and hypertrophic responsiveness during pre-cultivation with TGF-beta were investigated. Isolated adult ventricular cardiomyocytes from rats were either cultured in 20% (v/v) foetal calf serum (FCS) to activate autocrine released TGF-beta or used without pre-treatment. Protein synthesis was analysed by (14)C-phenylalanine incorporation. Expression of signalling molecules was determined by immunoblotting. During cultivation of cardiomyocytes with active TGF-beta only the expression of p38 MAP-kinase increased. Subsequent stimulation of beta-adrenoceptors induced protein synthesis in a p38 MAP-kinase-dependent way. However, stimulation of beta-adrenoceptors activated p38 MAP-kinase irrespective of pre-treatment with TGF-beta. In the absence of this cytokine, hyperosmolarity or reconstitution of mechanical activity increased protein synthesis via p38 MAP-kinase activation in freshly isolated cells. In conclusion, activation of p38 MAP-kinase is a newly identified necessary signalling step required for beta-adrenoceptor induced hypertrophic growth. Like activation of adenyl cyclase, activation of p38 MAP-kinase is up-stream of the TGF-beta-induced coupling to the regulation of protein synthesis. Reconstitution of mechanical activity mimics the co-activation required and induced by TGF-beta.
 ...
PMID:p38 MAP-kinase in cultured adult rat ventricular cardiomyocytes: expression and involvement in hypertrophic signalling. 1592 79

Adenosine is produced during cellular hypoxia and apoptosis, resulting in elevated tissue levels at sites of injury. Adenosine is also known to regulate a number of cellular responses to injury, but its role in hepatic stellate cell (HSC) biology and liver fibrosis is poorly understood. We tested the effect of adenosine on the cytosolic Ca2+ concentration, chemotaxis, and upregulation of activation markers in HSCs. We showed that adenosine did not induce an increase in the cytosolic Ca2+ concentration in LX-2 cells and, in addition, inhibited increases in the cytosolic Ca2+ concentration in response to ATP and PDGF. Using a Transwell system, we showed that adenosine strongly inhibited PDGF-induced HSC chemotaxis in a dose-dependent manner. This inhibition was mediated via the A(2a) receptor, was reversible, was reproduced by forskolin, and was blocked by the adenylate cyclase inhibitor 2,5-dideoxyadenosine. Adenosine also upregulated the production of TGF-beta and collagen I mRNA. In conclusion, adenosine reversibly inhibits Ca2+ fluxes and chemotaxis of HSCs and upregulates TGF-beta and collagen I mRNA. We propose that adenosine provides 1) a "stop" signal to HSCs when they reach sites of tissue injury with high adenosine concentrations and 2) stimulates transdifferentiation of HSCs by upregulating collagen and TGF-beta production.
 ...
PMID:Adenosine inhibits cytosolic calcium signals and chemotaxis in hepatic stellate cells. 1705 61

Mammalian cell invasion by Trypanosoma cruzi is a complex process in which various parasite and host cell components interact, triggering the activation of signaling cascades and Ca2+ mobilization in both cells. Using metacyclic trypomastigotes (MT) generated in vitro and tissue culture-derived trypomastigotes (TCT), as counterparts of insect-borne and bloodstream parasites, respectively, the mechanisms of host cell invasion by T. cruzi have been partially elucidated. Distinct sets of molecules are engaged by MT and TCT to enter target cells. MT make use of surface glycoproteins with dual Ca2+ signaling activity, in a manner dependent of T. cruzi isolate. In highly infective MT, the binding of gp82 to its receptor triggers a signaling cascade involving protein tyrosine kinase, phospholipase C and production of inositol 1,4,5-triphosphate, whereas in poorly invasive MT, the mucin-like gp35/50 induces the activation of a signaling route in which adenylate cyclase, generation of cAMP and Ca2+ mobilization from acidocalcisomes are implicated. The host cell signaling pathways activated by MT remain to be determined. Differently from MT, the TCT surface molecules that bind to host cells as a prelude to invasion, such as the glycoproteins of gp85 family, appear to be devoid of signaling properties, but they may induce TCT enzymes, such as oligopeptidase B and cruzipain, to generate Ca2+ signaling factors of parasite or host cell origin. Host cell responses mediated by TGF-beta receptor or integrin family member may also be triggered by TCT. A more complete and detailed picture of T. cruzi invasion needs further investigations.
 ...
PMID:Trypanosoma cruzi: parasite and host cell signaling during the invasion process. 1851 43


<< Previous 1 2 3