Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMPs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1988

Comparison of the effects of forskolin and dibutyryl cyclic AMP in neuroblastoma cells: evidence that some of the actions of dibutyryl cyclic AMP are mediated by butyrate.

We have compared the effects of forskolin, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP, Bt2-cAMP), and butyrate on several aspects of neuroblastoma cell physiology. The morphology of Neuro 2A cells was similar after incubation with forskolin and Bt2-cAMP, which caused extensive neurite outgrowth, whereas in the presence of butyrate some rudimentary neurites were formed but they were not nearly as extensive. All compounds produced a dose-dependent inhibition of cell proliferation, but the effect of Bt2-cAMP was more marked than that caused by forskolin, thus showing that the effect of Bt2-cAMP is due partially to the butyrate released. Acetylcholinesterase activity was lower in the cells incubated with butyrate or Bt2-cAMP than in untreated cells or in forskolin-treated cells. This suggests that cyclic AMP does not play a role in the regulation of this enzyme. Bt2-cAMP produced histone acetylation, a well-known effect of butyrate in cultured cells, whereas forskolin did not affect this modification. Consequently, the levels of thyroid hormone receptor, a nuclear protein whose concentration is regulated by butyrate through changes in acetylation of chromatin proteins, were decreased in cells incubated with Bt2-cAMP or butyrate, but were unaffected by forskolin. Butyrate elevated the concentration of histone H1(0), a protein that increases in neuroblastoma cells as a result of different treatments that block cell division. The concentration of H1(0) in the cells treated with Bt2-cAMP was at a level intermediate between that found after treatment with butyrate and with forskolin. The present results clearly indicate that some of the effects of Bt2-cAMP on neuroblastoma cells can be attributed to the butyryl moiety of this compound rather than to the cyclic nucleotide itself.

Acetylation↗
PubMed2005

Amino acid sequence and antimicrobial activity of chitin-binding peptides, Pp-AMP 1 and Pp-AMP 2, from Japanese bamboo shoots (Phyllostachys pubescens).

Two novel chitin-binding peptides, designated Pp-AMP 1 and Pp-AMP 2, which had antimicrobial activity against pathogenic bacteria and fungi, were purified from Japanese bamboo shoots (Phyllostachys pubescens) by a simple procedure based on chitin affinity chromatography. They had the common structural features of the plant defensin family, but they could not be grouped in any type of that family. They showed a high degree of homology to mistletoe toxins.

Amino Acid Sequence↗
PubMed1991

Effects of pertussis toxin, dibutyryl-cyclic-AMP, bromo-cyclic-AMP and forskolin on the behavioural and electrocortical power spectrum changes induced by microinfusion of interleukin-2 into the locus coeruleus.

Human recombinant interleukin-2 and rat recombinant IL-2 microinjected into the locus coeruleus of rats, induced typical dose-dependent behavioural sedation and/or sleep and electrocortical synchronization. During sleep induced by this lymphokine a dose-dependent increase in total voltage power (0.25-16 Hz) as well as in the 0.25-3, 3-6 and 6-9 Hz frequency bands was observed. The behavioural and electrocortical effects of interleukin-2 were blocked in animals pretreated with anti-IL-2 monoclonal antibodies and with naloxone, whereas they were still evident in rats pretreated with yohimbine. In addition, the behavioural and electrocortical slow-wave sleep effects observed after the administration of interleukin-2 into the locus coeruleus were reduced significantly or antagonized completely by a previous pretreatment with pertussis toxin, forskolin, dibutyryl-cyclic-AMP and 8-bromo-cyclic-AMP. These results are consistent with the hypothesis that the behavioural and electrocortical changes of this lymphokine are mediated at locus coeruleus level via a guanine regulatory Gi protein coupling IL-2 specific receptors to the adenylate cyclase system.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Comparisons of heptaminol AMP amidate and dibutyryl cyclic AMP on murine splenocytes proliferation.

Hepataminol AMP amidate (HAA), a nucleotide derivative possessing immunopotentiating activities, inhibited the mitogen-induced proliferation of murine splenocytes in vitro at the higher concentrations. Concanavalin A-induced mitogenic response was inhibited to 65 and 15% of the control value by HAA at the concentrations of 10(-4) and 10(-3) M, respectively. HAA also inhibited phytohemagglutinin P and lipopolysaccharide-induced responses at the same concentrations. The pattern of inhibition of mitogen-induced responses by HAA at higher concentrations was found to be almost similar to that of dibutyryl cyclic AMP (DbcAMP). Both HAA and DbcAMP also inhibited the blastogenesis of spleen cells in one way mixed lymphocyte reaction.

Adenosine Monophosphate↗
PubMed1995

Second-site mutations in cyclic AMP-sensitive revertants of a Ka mutant of S49 mouse lymphoma cells reduce the affinity of regulatory subunit of cyclic AMP-dependent protein kinase for catalytic subunit.

Ka mutants of S49 mouse lymphoma cells are generally heterozygous for expression of wild-type and mutant regulatory (R) subunits of type I alpha cyclic AMP-(cAMP)-dependent protein kinase, where the mutant R subunit has a defect in cAMP-binding to one of two intrachain cAMP-binding sites. Several cAMP-sensitive revertants of such a Ka mutant were found previously to harbor second-site mutations in the mutant allele, and we have now identified three such mutations by sequence analysis of PCR-amplified cDNAs. The resulting amino acid changes were Ala98 to Thr, Gly179 to Arg, or Gly224 to Asp. The Ka mutation in these strains (Glu201 to Lys) eliminated cAMP-binding to the more aminoterminal cAMP-binding site (site A). None of the second-site mutations restored this activity in bacterially expressed recombinant R subunit. On the other hand, all three second-site mutations reduced the apparent affinity of the mutant R subunit for catalytic (C) subunit with the effects of the substitutions at Ala98 and Gly179 substantially greater than the effect of the substitution at Gly224. Patterns of phosphorylation and turnover of wild-type and mutant R subunits in intact revertant cells were consistent with reduced association of the doubly mutant subunits with C subunit, but the free mutant subunits apparently were more stable than free wild-type subunits. Differences in metabolic turnover of mutant and wild-type subunits did not correlate with the sensitivities of the isolated proteins to proteolytic cleavage.

Animals↗
PubMed1998

Adaptation in cyclic AMP signalling processes: a central role for cyclic AMP phosphodiesterases.

Cyclic AMP has provided the paradigm for the second messenger concept. Recent evidence has identified a complex array of isoforms of the enzymes involved in generation, destroying and transmitting the effects of this second messenger. These proteins provide a sophisticated system for organising cAMP signal transduction in specific intracellular compartments; for allowing integration with other signalling systems and for controlling the kinetics and hence reaction characteristics of cAMP signal transduction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Phorbol esters and cyclic AMP activate AMP deaminase in adult rat cardiac myocytes.

Using rapid deenergization as a probe for adenylate deaminase activity in intact adult rat cardiac myocytes, we have previously established that IMP formation is enhanced by alpha-adrenergic agonists. In the present study, the effect of adrenergic agents on adenylate deaminase was further characterized. Phenylephrine (PE)3 increased IMP production in a dose-dependent fashion with an EC50 of 8 x 10(-7) M. The response to PE was reversed within 10 min by the alpha 1-antagonist, prazosin. Likewise, adenylate deaminase was also activated in ventricular myocytes challenged with phorbol 12-myristate 13-acetate (PMA, EC50 = 5 nM); cardiac cells presented with 100 nM PMA increased IMP production from 4.4 +/- 0.5 (control) to 15.7 +/- 0.9 nmol/mg protein when subsequently deenergized. The effects of PMA and PE were attenuated 85 +/- 5% and 96 +/- 4%, respectively, by pretreatment of cells with 150 nM staurosporine, an inhibitor of protein kinase C. Furthermore, incubation of cardiac cells with 1 microM PMA for 24 h blunted the response to both PMA and phenylephrine 85-90%. Elevating cyclic AMP (cAMP) content to greater than 15 pmol/mg by treatment with forskolin or isoproterenol plus isobutylmethylxanthine also resulted in enhanced adenylate deaminase activity, but this stimulatory effect was not abolished by 24 h incubation with 5 microM PMA. Forskolin and PMA-induced increases in IMP production appeared to be additive. However, 0.5 microM isoproterenol inhibited the cellular response to phenylephrine by about 30% but did not affect PMA-stimulated adenylate deaminase activity. We conclude that both cAMP and protein kinase C stimulate adenylate deaminase, perhaps through selective activation of different isoforms. However, cAMP also exerts partial inhibition on alpha-adrenoreceptor-mediated increases in IMP production.

AMP Deaminase↗
PubMed1990

Insulin alters the target size of the peripheral cyclic AMP phosphodiesterase but not the integral cyclic GMP-stimulated cyclic AMP phosphodiesterase in liver plasma membranes.

Radiation inactivation of the two high affinity cyclic AMP phosphodiesterases (PDE) found in liver plasma membranes afforded an estimation of their molecular target sizes in situ. The activity of the peripheral plasma membrane PDE decayed as a single exponential with a target size corresponding to a monomer of circa 54 kDa. The integral, cyclic GMP-stimulated PDE decayed as a dimer of circa 125 kDa. Preincubation of plasma membranes with insulin (10nM), prior to irradiation, caused the target size of only the peripheral plasma membrane PDE to increase. We suggest that insulin addition causes the peripheral plasma membrane PDE to alter its coupling to an integral plasma membrane protein with a target size of circa 90 kDa.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness.

Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

19F n.m.r. studies of conformational changes accompanying cyclic AMP binding to 3-fluorophenylalanine-containing cyclic AMP receptor protein from Escherichia coli.

A fluorine-containing analogue of the cyclic AMP (cAMP) receptor protein (CRP) from Escherichia coli was prepared by biosynthetic incorporation of 3-fluorophenylalanine (3-F-Phe). 19F n.m.r. studies on this protein have provided direct evidence for cAMP-induced conformational changes not only within the cAMP-binding domain but also within the hinge region connecting the cAMP-binding domain to the DNA-binding headpiece. At 313 K, the 19F n.m.r. spectrum of [3-F-Phe]CRP showed five signals corresponding to the five phenylalanine residues as expected for a symmetrical dimer. Proteolysis of [3-F-Phe]CRP with subtilisin produced a fragment (the alpha-fragment) containing the cAMP-binding domain. The alpha-fragment contains all the phenylalanines except for Phe-136, a residue located in the hinge region. By comparing the 19F spectra of [3-F-Phe]CRP and its alpha-fragment, the signal for Phe-136 was assigned. The chemical shifts of the corresponding signals in the two spectra are similar, indicating that the alpha-fragment retains the structure it has in the intact protein. The largest cAMP-induced shift was observed for the signal from Phe-136 providing direct evidence for a conformational change in the hinge region. However, whereas binding of a single cAMP molecule to a CRP dimer is known to be sufficient to activate the DNA binding, the n.m.r. data indicate that the hinge region does not have the same conformation in both subunits when only one cAMP molecule is bound.

Bacterial Proteins↗
PubMed1996

Transcriptional induction of the human renin gene by cyclic AMP requires cyclic AMP response element-binding protein (CREB) and a factor binding a pituitary-specific trans-acting factor (Pit-1) motif.

To delineate the cis-acting elements of the proximal promoter responsible for cyclic AMP (cAMP)-induced human renin gene transcription, 5'-flanking regions of the human renin gene were fused to a luciferase reporter gene and transfected in chorionic cells. Forskolin treatment induced the expression of luciferase by 2.4-fold when the reporter plasmid contained the promoter region (-582 to + 16). Mutation or deletion of the cAMP response element (CRE) diminished (1.7-fold) but did not abolish cAMP-induced transcription, demonstrating that the (-582 to -145) region containing the CRE and the region (-145 to -38) containing a Pit-1 (pituitary-specific trans-acting factor) site were both necessary for cAMP maximal induction. To study the molecular events mediating the cAMP induction, DNase I footprinting and electromobility shift assays (EMSAs) were performed with renin-producing chorionic cell and kidney cortex cell nuclear extracts, showing that the CRE-binding protein (CREB) interacts with the CRE and that tissue-specific factors, distinct from Pit-1, specifically bind the renin Pit-1 motif. Taken together, these results demonstrate that the cAMP response of the human renin gene may involve CREB binding the CRE and tissue-specific factors, different from Pit-1, that interact with the Pit-1 response DNA elements.

Base Sequence↗
PubMed1994

Cyclic AMP-dependent protein kinase regulates basal and cyclic AMP-stimulated but not phorbol ester-stimulated transcription of the tyrosine hydroxylase gene.

To define the precise role of cyclic AMP (cAMP)-dependent protein kinase (PKA) in transcriptional regulation of the tyrosine hydroxylase (TH) gene, we performed transient cotransfection analyses of a reporter construct containing the upstream 2,400 bp sequence of the rat TH gene with expression plasmids encoding a heat-stable specific inhibitor of PKA (PKI), a mutant regulatory subunit of PKA, or the catalytic subunit of PKA. Inhibition of PKA activity by expression of either PKI or mutant regulatory subunit blocked cAMP-stimulated induction and reduced basal transcription of the TH-reporter construct. Expression of the catalytic subunit of PKA induced the expression of the TH-reporter construct up to 50-fold in a dose-dependent manner. Primer extension analysis confirmed that PKA-mediated induction of TH-reporter expression occurred at the correct transcription initiation site. Expression of PKI did not affect induction following phorbol ester treatment, suggesting that PKA and protein kinase C (PKC) induce TH transcription by independent mechanisms. Finally, a double mutation within the cAMP response element (CRE) of TH2400-CAT diminished its basal and forskolin-stimulated transcription to the level of the promoterless plasmid, pBLCAT3, but did not alter the induction following treatment with phorbol ester, indicating that the CRE is not required for PKC-mediated transcriptional induction. Our results indicate that PKA, via the CRE, plays a crucial role for basal and cAMP-inducible transcription of the TH gene.

Base Sequence↗
PubMed1999

Phosphorylation-mediated activation and translocation of the cyclic AMP-specific phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase and mitogen-activated protein kinases. A potential mechanism allowing for the coordinated regulation of PDE4D activity and targeting.

In this study, we describe a novel mechanism by which a protein kinase C (PKC)-mediated activation of the Raf-extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) cascade regulates the activity and membrane targeting of members of the cyclic AMP-specific phosphodiesterase D family (PDE4D). Using a combination of pharmacological and biochemical approaches, we show that increases in intracellular cAMP cause a protein kinase A-mediated phosphorylation and activation of the two PDE4D variants expressed in vascular smooth muscle cells, namely PDE4D3 and PDE4D5. In addition, we show that stimulation of PKC via the associated activation of the Raf-MEK-ERK cascade results in the phosphorylation and activation of PDE4D3 in these cells. Furthermore, our studies demonstrate that simultaneous activation of both the protein kinase A and PKC-Raf-MEK-ERK pathways allows for a coordinated activation of PDE4D3 and for the translocation of the particulate PDE4D3 to the cytosolic fraction of these cells. These data are presented and discussed in the context of the activation of the Raf-MEK-ERK cascade acting to modulate the activation and subcellular targeting of PDE4D gene products mediated by cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis In 3T3-L1 adipocytes.

AMP-activated protein kinase (AMPK) is a phylogenetically conserved intracellular energy sensor that has been implicated as a major regulator of glucose and lipid metabolism in mammals. However, its possible role in mediating or influencing the adrenergic control of lipolysis in adipocytes remains uncertain. In this study, we utilized the murine cultured preadipocyte line 3T3-L1 to examine this question. Treatment of adipocytes with isoproterenol or forskolin promoted the phosphorylation of AMPK at a critical activating Thr-172 residue in a dose- and time-dependent manner. This correlated well with a stimulation of the activity of AMPK, as measured in the immune complex. Analogs of cAMP mimicked the effect of isoproterenol and forskolin on AMPK phosphorylation. Treatment of adipocytes with insulin reduced both basal and forskolin-induced AMPK phosphorylation via a pathway dependent on phosphatidylinositol 3'-kinase. Overexpression of a dominant-inhibitory mutant of AMPK blocked isoproterenol-induced lipolysis by approximately 50%. These data indicate that there exists a novel pathway by which cAMP can lead to the activation of AMPK, and in adipocytes, this is required for maximal activation of lipolysis.

3T3-L1 Cells↗
PubMed1999

Inhibition of cyclic AMP response element-binding protein/cyclic AMP response element-mediated transcription by the immunosuppressive drugs cyclosporin A and FK506 depends on the promoter context.

The immunosuppressants cyclosporin A and FK506 (tacrolimus) can block the phosphatase calcineurin, thereby inhibiting gene transcription directed by the cyclic AMP (cAMP)- and calcium-responsive transcription factor, cAMP response element (CRE)-binding protein, and its binding site, CRE, in various cell lines. This action is a novel molecular mechanism of cyclosporin A and FK506 action. Because inhibition of CREB/CRE-directed transcription by cyclosporin A and FK506 has previously been observed by using synthetic minienhancers, reporter fusion genes were constructed to examine the effect of cyclosporin A and FK506 on the transcriptional activity of CRE-containing natural promoters. In transient transfection experiments, cyclosporin A and FK506 inhibited the transcriptional activation by cAMP and the membrane depolarization of three CRE-containing promoters. However, cyclosporin A and FK506 failed to inhibit the activation by cAMP of another promoter, the rat insulin I gene promoter. The lack of cyclosporin A/FK506 sensitivity is not intrinsic to the insulin CRE because cyclosporin A and FK506 inhibited the activation by cAMP of the insulin CRE when isolated and used as a synthetic minienhancer. Rather, cyclosporin A/FK506 resistance may be conferred by specific promoter interactions because a mutational analysis of the insulin promoter revealed that inside this promoter, CRE activity depends on an adjacent control element. These data show that cyclosporin A and FK506 can inhibit CRE activity when the CRE resides in its natural promoter. However, the cyclosporin A/FK506 sensitivity depends on the specific promoter context. The results suggest that cyclosporin A and FK506 may alter target tissue function through the regulation of a subset of CRE-containing genes.

Animals↗
PubMed2003

Cyclic AMP inhibition of tumor necrosis factor alpha production induced by amyloidogenic C-terminal peptide of Alzheimer's amyloid precursor protein in macrophages: involvement of multiple intracellular pathways and cyclic AMP response element binding protein.

In the present study, we focused on the molecular events involved in tumor necrosis factor-alpha (TNF-alpha) production in response to the amyloidogenic 105-amino acid carboxyl-terminal fragment (CT105) of amyloid precursor protein, a candidate alternative toxic element in Alzheimer's disease pathology, and the mechanisms by which cyclic AMP regulates the relating inflammatory signal cascades. CT105 at nanomolar concentrations strongly activated multiple signaling pathways involving tyrosine kinase-dependent extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Moreover, phosphatidylinositol 3-kinase/Akt signal was required for excess TNF-alpha production in human macrophages derived from THP-1 cells. Interferon-gamma significantly potentiated the induction of the CT105-mediated signal cascade. These multiple signaling pathways in turn converged, at least in part, at the nuclear transcription factor known as cAMP response element binding protein (CREB), which acts on the TNF-alpha gene promoter through the cAMP response element. The cell-permeable cAMP analog dibutyryl cAMP partially and almost simultaneously suppressed all of these CT105-induced signaling pathways through excessive CREB phosphorylation, which led to decreased CREB DNA binding activity and reduced TNF-alpha expression. Furthermore, dibutyryl cAMP decreased the interaction of the p65 nuclear factor-kappa B with CREB binding protein, thus further inhibiting CT105-mediated TNF-alpha expression. Collectively, the detailed molecular mechanisms of amyloidogenic CT-induced TNF-alpha production as negatively regulated by cAMP may advance the possibility of targeted treatment in Alzheimer's disease.

Alzheimer Disease↗
PubMed1985

Control of Vibrio fischeri luminescence gene expression in Escherichia coli by cyclic AMP and cyclic AMP receptor protein.

Under certain conditions glucose represses the autoinducible synthesis of luminescence enzymes in Vibrio fischeri. To examine the genetic regulation of luminescence more closely, Escherichia coli catabolite repression mutants were transformed with a plasmid (pJE202) that contains V. fischeri genes specifying the luminescence enzymes and encoding regulatory functions for luminescence (the lux genes) or with plasmids (pJE413 and pJE455) containing transcriptional fusions between the lacZ gene on transposon mini-Mu and specific genes in each of the two lux operons. Unless cyclic AMP (cAMP) was added to the growth medium, an adenylate cyclase deletion mutant containing pJE202 produced very little light and low levels of the light-emitting enzyme luciferase. When grown in the presence or absence of cAMP, a cAMP receptor protein (CRP) deletion mutant produced low levels of light and luciferase. A mutant that does not make cAMP but does make an altered CRP which does not require cAMP for activity produced induced levels of luminescence after transformation with pJE202. To test the effects of cAMP and CRP on each of the two lux operons separately rather than on both together, the E. coli catabolite repression mutants were transformed with pJE413 and pJE455. From measurements of beta-galactosidase and luciferase activities it appeared that cAMP and CRP affected transcription of both lux operons. In the presence of autoinducer and its receptor, transcription of the operon encoding all of the luminescence genes except the receptor gene appeared to be activated by cAMP and CRP, whereas in the absence of the receptor, cAMP and CRP appeared to decrease transcription of this operon. Transcription of the operon encoding the autoinducer receptor appeared to be stimulated by cAMP and CRP in the absence of the receptor itself. These results demonstrate that cAMP and CRP are required for proper control of the V. fischeri luminescence system and suggest that lux gene transcription is required by a complex mechanism.

Cyclic AMP↗
PubMed1985

Negative regulation of adenylate cyclase gene (cya) expression by cyclic AMP-cyclic AMP receptor protein in Escherichia coli: studies with cya-lac protein and operon fusion plasmids.

We constructed cya-lac protein and operon fusion plasmids in vitro. The effect of cyclic AMP (cAMP) on cya expression was examined by measuring the synthesis of beta-galactosidase in Escherichia coli cells containing fused plasmids. In the cya-lacZ fused protein system, cya expression was strongly repressed by exogenous cAMP. Functional cAMP receptor protein (CRP) was necessary for this effect. On the other hand, in a tet-lacZ fused protein as a control system, tet expression was not affected by cAMP. The inhibition of cya expression by cAMP was also observed in the cya-lac fused operon system, although it was necessary to increase the amount of cAMP or CRP in the cells to detect the effect. The results indicate that cAMP-CRP is a negative regulator of cya expression at the level of transcription.

Adenylyl Cyclases↗