scholarly journals Modulation of Cyclic AMP Levels in Fallopian Tube Cells by Natural and Environmental Estrogens

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1250
Author(s):  
Marinella Rosselli ◽  
Barbara P. S. Cometti ◽  
Brigitte Leeners ◽  
Marta Ewa Szutkowska ◽  
Edwin K. Jackson ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Fallopian Tube ◽  
Early Embryo ◽  
Environmental Estrogens ◽  
Intracellular Camp ◽  
Paracrine Factors ◽  
Creb Phosphorylation ◽  
Adrenoceptor Agonist ◽  
17Β Estradiol ◽  
Camp Levels

Autocrine/paracrine factors generated in response to 17β-estradiol (E2) within the fallopian tube (FT) facilitate fertilization and early embryo development for implantation. Since cyclic AMP (cAMP) plays a key role in reproduction, regulation of its synthesis by E2 may be of biological/pathophysiological relevance. Herein, we investigated whether cAMP production in FT cells (FTCs) is regulated by E2 and environmental estrogens (EE’s; xenoestrogens and phytoestrogens). Under basal conditions, low levels of extracellular cAMP were detectable in bovine FTCs (epithelial cells and fibroblasts; 1:1 ratio). Treatment of FTCs with forskolin (AC; adenylyl cyclase activator), isoproterenol (β-adrenoceptor agonist) and IBMX (phosphodiesterase (PDE) inhibitor) dramatically (>10 fold) increased cAMP; whereas LRE1 (sAC; soluble AC inhibitor) and 2’,5’-dideoxyadenosine (DDA; transmembrane AC (tmAC)) inhibitor decreased cAMP. Comparable changes in basal and stimulated intracellular cAMP were also observed. Ro-20-1724 (PDE-IV inhibitor), but not milrinone (PDE-III inhibitor) nor mmIBMX (PDE-I inhibitor), augmented forskolin-stimulated cAMP levels, suggesting that PDE-IV dominates in FTCs. E2 increased cAMP levels and CREB phosphorylation in FTCs, and these effects were mimicked by EE’s (genistein, 4-hydroxy-2’,4’,6’-trichlorobiphenyl, 4-hydroxy-2’,4’,6’-dichlorobiphenyl). Moreover, the effects of E2 and EE were blocked by the tmAC inhibitor DDA, but not by the ERα/β antagonist ICI182780. Moreover, BAPTA-AM (intracellular-Ca2+ chelator) abrogated the effects of E2, but not genistein, on cAMP suggesting differential involvement of Ca2+. Treatment with non-permeable E2-BSA induced cAMP levels and CREB-phosphorylation; moreover, the stimulatory effects of E2 and EEs on cAMP were blocked by G15, a G protein-coupled estrogen receptor (GPER) antagonist. E2 and IBMX induced cAMP formation was inhibited by LRE1 and DDA suggesting involvement of both tmAC and sAC. Our results provide the first evidence that in FTCs, E2 and EE’s stimulate cAMP synthesis via GPER. Exposure of the FT to EE’s and PDE inhibitors may result in abnormal non-cyclic induction of cAMP levels which may induce deleterious effects on reproduction.

scholarly journals Cyclic AMP enhances the sexual agglutinability of Chlamydomonas flagella.

1989 ◽  
Vol 109 (1) ◽  
pp. 247-252 ◽  
Author(s):  
U W Goodenough
Keyword(s):  
Cell Wall ◽  
Cyclic Amp ◽  
Mating Type ◽  
Feedback System ◽  
Intracellular Camp ◽  
Camp Generation ◽  
Sexual Agglutinability ◽  
Single Mating ◽  
Wall Loss ◽  
Camp Levels

Sexual adhesion between Chlamydomonas reinhardtii gametes elicits a rise in intracellular cAMP levels, and exogenous elevation of intracellular cAMP levels in gametes of a single mating type induces such mating responses as cell wall loss, flagellar tip activation, and mating structure activation (Pasquale, S. M., and U. W. Goodenough. 1987. J. Cell Biol. 105:2279-2292). Here evidence is presented that sexual adhesion mobilizes agglutinin to the flagellar surface, and that this mobilization can be induced by exogenous presentation of cAMP to gametes of a single mating type. It is proposed that Chlamydomonas adhesion entails a positive feedback system--initial contacts stimulate the presentation of additional agglutinin--and that this feedback is mediated by adhesion-induced cAMP generation.

scholarly journals Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells.

1976 ◽  
Vol 71 (2) ◽  
pp. 515-534 ◽  
Author(s):  
C E Zeilig ◽  
R A Johnson ◽  
E W Sutherland ◽  
D L Friedman
Keyword(s):  
Cell Cycle ◽  
Cyclic Amp ◽  
Hela Cells ◽  
S Phase ◽  
Intracellular Camp ◽  
Specific Effects ◽  
Low Concentrations ◽  
High Concentrations ◽  
Camp Levels ◽  
Stimulation Of

The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations.

scholarly journals Cyclic AMP Promotes Neuronal Survival by Phosphorylation of Glycogen Synthase Kinase 3β

2000 ◽  
Vol 20 (24) ◽  
pp. 9356-9363 ◽  
Author(s):  
Mingtao Li ◽  
Xiaomin Wang ◽  
Mary Kay Meintzer ◽  
Tracey Laessig ◽  
Morris J. Birnbaum ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Glycogen Synthase ◽  
Neuronal Survival ◽  
Glycogen Synthase Kinase ◽  
Intracellular Camp ◽  
Glycogen Synthase Kinase 3Β ◽  
Gsk 3Β ◽  
Camp Levels

ABSTRACT Agents that elevate intracellular cyclic AMP (cAMP) levels promote neuronal survival in a manner independent of neurotrophic factors. Inhibitors of phosphatidylinositol 3 kinase and dominant-inactive mutants of the protein kinase Akt do not block the survival effects of cAMP, suggesting that another signaling pathway is involved. In this report, we demonstrate that elevation of intracellular cAMP levels in rat cerebellar granule neurons leads to phosphorylation and inhibition of glycogen synthase kinase 3β (GSK-3β). The increased phosphorylation of GSK-3β by protein kinase A (PKA) occurs at serine 9, the same site phosphorylated by Akt. Purified PKA is able to phosphorylate recombinant GSK-3β in vitro. Inhibitors of GSK-3 block apoptosis in these neurons, and transfection of neurons with a GSK-3β mutant that cannot be phosphorylated interferes with the prosurvival effects of cAMP. These data suggest that activated PKA directly phosphorylates GSK-3β and inhibits its apoptotic activity in neurons.

scholarly journals A 3′,5′ Cyclic AMP (cAMP) Phosphodiesterase Modulates cAMP Levels and Optimizes Competence in Haemophilus influenzae Rd

1998 ◽  
Vol 180 (17) ◽  
pp. 4401-4405 ◽  
Author(s):  
Leah P. Macfadyen ◽  
Caixia Ma ◽  
Rosemary J. Redfield
Keyword(s):  
Cyclic Amp ◽  
Haemophilus Influenzae ◽  
Competence Development ◽  
Intracellular Camp ◽  
Camp Phosphodiesterase ◽  
E Coli ◽  
Sugar Fermentation ◽  
Endogenous Production ◽  
Camp Levels ◽  
Dependent Processes

ABSTRACT Changes in intracellular 3′,5′ cyclic AMP (cAMP) concentration regulate the development of natural competence inHaemophilus influenzae. In Escherichia coli, cAMP levels are modulated by a cAMP phosphodiesterase encoded by the cpdA gene. We have used several approaches to demonstrate that the homologous icc gene of H. influenzae encodes a functional cAMP phosphodiesterase and that this gene limits intracellular cAMP and thereby influences competence and other cAMP-dependent processes. In E. coli, expression of cloned icc reduced both cAMP-dependent sugar fermentation and β-galactosidase expression, as has been shown forcpdA. In H. influenzae, an icc null mutation increased cAMP-dependent sugar fermentation and competence development in strains where these processes are limited by mutations reducing cAMP synthesis. When endogenous production of cAMP was eliminated by a cya mutation, an icc strain was 10,000-fold more sensitive to exogenous cAMP than anicc + strain. The icc strain showed moderately elevated competence under noninducing conditions, as expected, but had subnormal competence increases at onset of stationary phase in rich medium, and on transfer to a nutrient-limited medium, suggesting that excessive cAMP may interfere with induction. Consistent with this finding, a cya strain cultured in 1 mM cAMP failed to develop maximal competence on transfer to inducing conditions. Thus, by limiting cAMP levels, the H. influenzae cAMP phosphodiesterase may coordinate its responses to nutritional stress, ensuring optimal competence development.

Forskolin and thyrotrophin stimulation of rat FRTL-5 thyroid cell growth: the role of cyclic AMP

1987 ◽  
Vol 114 (2) ◽  
pp. 199-205 ◽  
Author(s):  
P. A. Ealey ◽  
C. A. Ahene ◽  
J. M. Emmerson ◽  
N. J. Marshall
Keyword(s):  
Cyclic Amp ◽  
Dose Range ◽  
Phosphodiesterase Inhibitor ◽  
Lag Phase ◽  
Thyroid Cell ◽  
Intracellular Camp ◽  
Camp Levels ◽  
Tsh Stimulation ◽  
Stimulation Of

ABSTRACT The adenylate cyclase stimulator forskolin increases intracellular cyclic AMP (cAMP) in rat FRTL-5 cells within minutes and, after a lag phase of 20–24 h, an increase of cells in metaphase is seen. The dose– response relationships were similar in both systems, with significant increases in the number of metaphases observed at ∼0·1 μmol/l and a doubling of cAMP levels at 1 μmol/l, whilst doses of 0·1 mmol/l and above proved cytotoxic. An involvement of intracellular cAMP as a positive intermediate in cell division was further suggested by the finding that a low dose of forskolin (0·1 μmol/l) potentiated TSH stimulation of mitosis. Isobutyl methyl xanthine (IBMX), a phosphodiesterase inhibitor, also acted as a mitogen and potentiated TSH action. Moreover, the simultaneous inclusion of low doses of IBMX and forskolin additionally potentiated TSH stimulation of mitosis. An analogue of cAMP, dibutyryl cAMP, also stimulated mitosis and acted over a restricted dose range, with maximal stimulation at 1 mmol/l. We conclude that cAMP may act as a positive signal for FRTL-5 thyroid cell proliferation. J. Endocr. (1987) 114, 199–205

scholarly journals Modulation of cAMP levels by a conserved actinobacteria phosphodiesterase enzyme reduces antimicrobial tolerance in mycobacteria

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Michael Thomson ◽  
Gerald Larrouy-Maumus
Keyword(s):  
Gene Expression ◽  
Antimicrobial Resistance ◽  
Cyclic Amp ◽  
Cell Envelope ◽  
Model Organism ◽  
Intracellular Camp ◽  
Virulence Regulation ◽  
Regulation Of Metabolism ◽  
Altered Cell ◽  
Camp Levels

Antimicrobial tolerance is the gateway to the development of antimicrobial resistance and is therefore a major issue that needs to be tackled. The second messenger, cyclic-AMP (cAMP) is conserved across all taxa of life. It is involved in propagating the signal from environmental stimuli and converting it into a response. In bacteria such as M. tuberculosis (Mtb), P. aeruginosa, V. cholerae and B. pertussis, cAMP has been implicated in virulence, regulation of metabolism and gene expression. Cyclic AMP signalling in mycobacteria is especially complex – with 16 enzymes that produce cAMP in Mtb alone. By discovery of a novel, actinobacteria conserved enzyme that degrades cAMP, we have developed a tool to modulate cAMP levels in mycobacteria. By using a combination of metabolomics, bioenergetics and time-to-kill assays, we show that when this enzyme is overexpressed in the model organism M. smegmatis, there is a 3.3 -fold decrease in intracellular cAMP levels. This was concomitant with 7-fold increased ATP. The unbalanced ATP/cAMP ratio consequently altered cell envelope permeability, compromised bioenergetics and most importantly, led to a decrease in the tolerance to various frontline antimicrobials. Taken together, this work provides clear evidence that cAMP is involved in antimicrobial tolerance in mycobacteria and that this may represent a promising new target for antimicrobial development.

scholarly journals . Effect of fluoxetine on the inhibition of adenylate cyclase activity in foskolin-stimulated MLTC-1 leydig cells

2020 ◽  
Vol 17 (4) ◽  
pp. 595-602
Author(s):  
Nguyen Thi Mong Diep ◽  
Nguyen Thi Bich Hang ◽  
Nguyen Le Cong Minh ◽  
Tran Thanh Son ◽  
Nguyen Thuy Duong
Keyword(s):  
Cyclic Amp ◽  
Leydig Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cell Types ◽  
Intracellular Camp ◽  
Atp Levels ◽  
Long Time ◽  
Short Time ◽  
Camp Levels

Fluoxetine (FLX), a widely used antidepressant primarily acting as a selective serotonin reuptake inhibitor, has been shown to exhibit other mechanisms of action in various cell types. Cyclic adenosine monophosphate (cAMP) is a second messenger used for intracellular signal induction. Cyclic AMP is a nucleotide synthesized within the cell from adenosine triphosphate by the adenylyl cyclase enzyme, and is inactivated enzymatically to 5′AMP by hydroxylation with a group of enzymes called phosphodiesterase. The aim of this study was to determine the effects of FLX on MLTC-1 Leydig cells on intracellular cyclic AMP response to forskolin (FSK). MLTC-1 cells were incubated at 37°C in media supplemented with or without different doses of FLX (0, 0.156, 0.3125, 0.625, 1.25, 2.5, 5 and 10 µM). We then looked for how the concentration of FLX for a short-time (2 hours) and a long-time (24 hours) affects the concentration of intracellular cyclic AMP response to FSK and ATP levels on MLTC-1 cells. Our results show that FLX decreased the intracellular cAMP response to FSK depending on FLX concentration. FLX decreased significantly cAMP levels only at 10 µM after 2 hours of incubation but after 24 hours of incubation FLX caused an effect on cAMP levels at 5 µM and at 10 µM. Moreover, as expected, FLX also caused a decline of steroidogenesis, which is under the control of cAMP and ATP levels in the cells. Taken together, these findings demonstrate that the inhibition of cAMP synthesis by FLX is dose-dependent, and that FLX also inhibited hormone-induced steroidogenesis in MLTC-1 cells.

scholarly journals Cyclic AMP inhibits Cl-/HCO3- exchange at the apical membrane of Necturus gallbladder epithelium.

1987 ◽  
Vol 90 (2) ◽  
pp. 173-196 ◽  
Author(s):  
L Reuss
Keyword(s):  
Cyclic Amp ◽  
Apical Membrane ◽  
Phosphodiesterase Inhibitor ◽  
Intracellular Camp ◽  
Bathing Solution ◽  
Gallbladder Epithelium ◽  
Bathing Medium ◽  
Necturus Gallbladder ◽  
Mechanism Of Inhibition ◽  
Camp Levels

Intracellular microelectrode techniques were employed to study the effect of cyclic AMP on apical membrane Cl-/HCO3- exchange and electrodiffusive HCO3- transport in Necturus gallbladder epithelium. Intracellular cAMP levels were raised by addition of either the phosphodiesterase inhibitor theophylline (3 X 10(-3) M) or the adenylate cyclase activator forskolin (10(-5) M) to the serosal bathing solution. Measurements of pH in a poorly buffered control mucosal solution upon stopping superfusion show acidification, owing to secretion of both H+ and HCO3-. When the same experiment is performed after addition of amiloride or removal of Na+ from the mucosal bathing medium, alkalinization is observed since H+ transport is either inhibited or reversed, whereas HCO3- secretion persists. The changes in pH in both amiloride or Na-free medium were significantly decreased in theophylline-treated tissues. Theophylline had no effect on the initial rates of fall of intracellular Cl- activity (aCli) upon reducing mucosal solution [Cl-] to either 10 or 0 mM, although membrane voltage and resistance measurements were consistent with stimulation of apical membrane electrodiffusive Cl- permeability. Estimates of the conductive flux, obtained by either reducing simultaneously mucosal [Cl-] and [HCO3-] or lowering [Cl-] alone in the presence of a blocker of anion exchange (diphenylamine-2-carboxylate), indicate that elevation of intracellular cAMP inhibited the anion exchanger by approximately 50%. Measurements of net Cl- uptake upon increasing mucosal Cl- from nominally zero to levels ranging from 2.5 to 100 mM suggest that the mechanism of inhibition is a decrease in Vmax. Consistent with these results, the rate of intracellular alkalinization upon reducing external Cl- was also inhibited significantly by theophylline. Reducing mucosal solution [HCO3-] from 10 to 1 mM under control conditions caused intracellular acidification and an increase in aCli. Theophylline inhibited both changes, by 62 and 32%, respectively. These data indicate that elevation of intracellular cAMP inhibits apical membrane anion (Cl-/HCO3-) exchange. Studies of the effects of rapid changes in mucosal [HCO3-] on membrane voltages and the apparent ratio of membrane resistances, both in the presence and in the absence of theophylline, with or without Cl- in the mucosal solution, do not support the hypothesis that cAMP produces a sizable increase in apical membrane electrodiffusive HCO3- permeability.

scholarly journals Cyclic AMP in Mycobacteria: Characterization and Functional Role of the Rv1647 Ortholog in Mycobacterium smegmatis

2008 ◽  
Vol 190 (11) ◽  
pp. 3824-3834 ◽  
Author(s):  
Bob Kennedy M. Dass ◽  
Ritu Sharma ◽  
Avinash R. Shenoy ◽  
Rohini Mattoo ◽  
Sandhya S. Visweswariah
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
Mycobacterium Smegmatis ◽  
Functional Characterization ◽  
Acid Stress ◽  
Logarithmic Phase ◽  
Intracellular Camp ◽  
Genes Encoding ◽  
Camp Levels

ABSTRACT Mycobacterial genomes are endowed with many eukaryote-like nucleotide cyclase genes encoding proteins that can synthesize 3′,5′-cyclic AMP (cAMP). However, the roles of cAMP and the need for such redundancy in terms of adenylyl cyclase genes remain unknown. We measured cAMP levels in Mycobacterium smegmatis during growth and under various stress conditions and report the first biochemical and functional characterization of the MSMEG_3780 adenylyl cyclase, whose orthologs in Mycobacterium tuberculosis (Rv1647) and Mycobacterium leprae (ML1399) have been recently characterized in vitro. MSMEG_3780 was important for producing cAMP levels in the logarithmic phase of growth, since the ΔMSMEG_3780 strain showed lower intracellular cAMP levels at this stage of growth. cAMP levels decreased in wild-type M. smegmatis under conditions of acid stress but not in the ΔMSMEG_3780 strain. This was correlated with a reduction in MSMEG_3780 promoter activity, indicating that the effect of the reduction in cAMP levels on acid stress was caused by a decrease in the transcription of MSMEG_3780. Complementation of the ΔMSMEG_3780 strain with the genomic integration of MSMEG_3780 or the Rv1647 gene could restore cAMP levels during logarithmic growth. The Rv1647 promoter was also acid sensitive, emphasizing the biochemical and functional similarities in these two adenylyl cyclases. This study therefore represents the first detailed biochemical and functional analysis of an adenylyl cyclase that is important for maintaining cAMP levels in mycobacteria and underscores the subtle roles that these genes may play in the physiology of the organism.

Transmembrane Calcium Influx Associated with von Willebrand Factor Binding to GP Ib in the Initiation of Shear-Induced Platelet Aggregation

1993 ◽  
Vol 69 (05) ◽  
pp. 496-502 ◽  
Author(s):  
Yasuo Ikeda ◽  
Makoto Handa ◽  
Tetsuji Kamata ◽  
Koichi Kawano ◽  
Yohko Kawai ◽  
...  
Keyword(s):  
Shear Force ◽  
Calcium Influx ◽  
Fold Increase ◽  
Intracellular Camp ◽  
Recombinant Fragment ◽  
Transmembrane Flux ◽  
Irreversible Aggregation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Camp Levels

SummaryWe found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two-to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+]i increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+]i and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.

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