Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release

2001 ◽  
Vol 281 (4) ◽  
pp. C1158-C1164 ◽  
Author(s):  
Randy S. Sprague ◽  
Mary L. Ellsworth ◽  
Alan H. Stephenson ◽  
Andrew J. Lonigro
Keyword(s):  
Signal Transduction ◽  
Adenylyl Cyclase ◽  
Atp Release ◽  
Signal Transduction Pathway ◽  
Intracellular Camp ◽  
Transmembrane Conductance Regulator ◽  
Transduction Pathway ◽  
Camp Analog ◽  
Dependent Protein ◽  
Erythrocyte Deformation

Previously, we reported that red blood cells (RBCs) of rabbits and humans release ATP in response to mechanical deformation and that this release of ATP requires the activity of the cystic fibrosis transmembrane conductance regulator (CFTR). It was reported that cAMP, acting through a cAMP-dependent protein kinase, PKA, is an activator of CFTR. Here we investigate the hypothesis that cAMP stimulates ATP release from RBCs. Incubation of human and rabbit RBCs with the direct activator of adenylyl cyclase, forskolin (10 or 100 μM), with IBMX (100 μM), resulted in ATP release and increases in intracellular cAMP. In addition, epinephrine (1 μM), a receptor-mediated activator of adenylyl cyclase, stimulated ATP release from rabbit RBCs. Moreover, incubation of human and rabbit RBCs with an active cAMP analog [adenosine 3′5′-cyclic monophosphorothioate Sp-isomer (Sp-cAMP, 100 μM)] resulted in ATP release. In contrast, forskolin and Sp-cAMP were without effect on dog RBCs, cells known not to release ATP in response to deformation. When rabbit RBCs were incubated with the inactive cAMP analog and inhibitor of PKA activity, adenosine 3′,5′-cyclic monophosphorothioate Rp-isomer (100 μM), deformation-induced ATP release was attenuated. These results are consistent with the hypothesis that adenylyl cyclase and cAMP are components of a signal-transduction pathway relating RBC deformation to ATP release from human and rabbit RBCs.

Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1

1990 ◽  
Vol 10 (7) ◽  
pp. 3824-3827
Author(s):  
M Chedid ◽  
S B Mizel
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Interleukin 1 ◽  
Signal Transduction Pathway ◽  
Cell Types ◽  
Specific Protein ◽  
Transduction Pathway ◽  
Dependent Protein

Expression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat. This inhibitor did not affect protein kinase C-mediated gene transcription, suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types.

scholarly journals Wenxin-Keli Regulates the Calcium/Calmodulin-Dependent Protein Kinase II Signal Transduction Pathway and Inhibits Cardiac Arrhythmia in Rats with Myocardial Infarction

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Yanwei Xing ◽  
Yonghong Gao ◽  
Jianxin Chen ◽  
Haiyan Zhu ◽  
Aiming Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Signal Transduction ◽  
Protein Kinase ◽  
Signal Transduction Pathway ◽  
Treated Group ◽  
Transduction Pathway ◽  
Dependent Protein Kinase ◽  
Group A ◽  
Dependent Protein

Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of theα- andβ-adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction. A total of 100 healthy Sprague Dawley rats were used in the study. The rats were randomly divided into four groups (a sham group, a myocardial infarction (MI) group, a WXKL-treated group, and an amiodarone-treated group). A myocardial infarction model was established in these rats by ligating the left anterior descending coronary artery for 4 weeks. Western blotting was used to assess CaMKII, p-CaMKII (Thr-286), PLB, p-PLB (Thr-17), RYR2, and FK binding protein 12.6 (FKBP12.6) levels. The Ca2+content in the sarcoplasmic reticulum (SR) and the calcium transient amplitude were studied by confocal imaging using the fluorescent indicator Fura-4. In conclusion, WXKL may inhibit heart failure and cardiac arrhythmias by regulating the CaMKII signal transduction pathway similar to amiodarone.

scholarly journals Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1.

1990 ◽  
Vol 10 (7) ◽  
pp. 3824-3827 ◽  
Author(s):  
M Chedid ◽  
S B Mizel
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Interleukin 1 ◽  
Signal Transduction Pathway ◽  
Cell Types ◽  
Specific Protein ◽  
Transduction Pathway ◽  
Dependent Protein

Expression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat. This inhibitor did not affect protein kinase C-mediated gene transcription, suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types.

scholarly journals Cyclic nucleotides in glutamate chemosensory signal transduction of Paramecium

1997 ◽  
Vol 110 (20) ◽  
pp. 2567-2572
Author(s):  
W.Q. Yang ◽  
C. Braun ◽  
H. Plattner ◽  
J. Purvee ◽  
J.L. Van Houten
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Signal Transduction Pathway ◽  
Protein Kinase Inhibitors ◽  
Intracellular Camp ◽  
Paramecium Tetraurelia ◽  
Transduction Pathway ◽  
Kinetic Measurements ◽  
Chemosensory Transduction

Glutamate is an attractant stimulus to Paramecium tetraurelia. It causes a hyperpolarization of the cell and smooth, relatively fast swimming that is characteristic of hyperpolarizing stimuli. We show here that by 1–30 seconds of stimulation, glutamate increases intracellular cAMP. Interestingly, other attractant stimuli, such as acetate and NH4Cl, that similarly hyperpolarize the cell do not induce an increase in cyclic AMP observable at 30 seconds. In order to determine whether the changes in cyclic AMP could be rapid enough to participate in stimulation as compared to slower processes such as adaptation, rapid kinetic measurements of cyclic AMP were made on whole cells by quenched-flow. We found that, in cells stimulated with glutamate, intracellular cyclic AMP increases by 30 mseconds and peaks at about sevenfold over basal levels by 200 mseconds. Cyclic GMP does not change relative to basal levels over rapid or slower time courses of glutamate stimulation. An antagonist of glutamate, IMP, depolarizes the cells and decreases intracellular cyclic AMP by approx. 50% and slightly increases cyclic GMP. Results of behavioral tests of cells treated with protein kinase inhibitors also suggest that cyclic AMP is part of the signal transduction pathway for glutamate, but not for other attractant stimuli. These studies are the first demonstration of a possible role for cyclic nucleotide second messengers in an attractant chemosensory transduction pathway in Paramecium.

Heterotrimeric G protein Giis involved in a signal transduction pathway for ATP release from erythrocytes

2004 ◽  
Vol 286 (3) ◽  
pp. H940-H945 ◽  
Author(s):  
Jeffrey J. Olearczyk ◽  
Alan H. Stephenson ◽  
Andrew J. Lonigro ◽  
Randy S. Sprague
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Atp Release ◽  
Signal Transduction Pathway ◽  
Protein G ◽  
Transduction Pathway ◽  
Heterotrimeric G Proteins ◽  
Heterotrimeric G Protein

Erythrocytes are reported to release ATP in response to mechanical deformation and decreased oxygen tension. Previously we proposed that receptor-mediated activation of the heterotrimeric G protein Gsresulted in ATP release from erythrocytes. Here we investigate the hypothesis that activation of heterotrimeric G proteins of the Gisubtype are also involved in a signal transduction pathway for ATP release from rabbit erythrocytes. Heterotrimeric G proteins Gαi1, Gαi2, and Gαi3but not Gαowere identified in rabbit and human erythrocyte membranes. Pretreatment of rabbit erythrocytes with pertussis toxin (100 ng/ml, 2 h), which uncouples Gi/ofrom their effector proteins, inhibited deformation-induced ATP release. Incubation of rabbit and human erythrocytes with mastoparan (Mas, 10 μM) or Mas-7 (1 μM), which are compounds that directly activate Giproteins, resulted in ATP release. However, rabbit erythrocytes did not release ATP when incubated with Mas-17 (10 μM), which is an inactive Mas analog. In separate experiments, Mas (10 μM) but not Mas-17 (10 μM) increased intracellular concentrations of cAMP when incubated with rabbit erythrocytes. Importantly, Mas-induced ATP release from rabbit erythrocytes was inhibited after treatment with pertussis toxin (100 ng/ml, 2 h). These data are consistent with the hypothesis that the heterotrimeric G protein Giis a component of a signal transduction pathway for ATP release from erythrocytes.

scholarly journals Function of the ste signal transduction pathway for mating pheromones sustains MAT alpha 1 transcription in Saccharomyces cerevisiae.

1993 ◽  
Vol 13 (4) ◽  
pp. 2050-2060 ◽  
Author(s):  
Y Mukai ◽  
S Harashima ◽  
Y Oshima
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Single Copy ◽  
Upstream Region ◽  
Transduction Pathway ◽  
Mating Ability ◽  
Mating Pheromones ◽  
C Terminus ◽  
Dependent Protein

Sterile mutants of Saccharomyces cerevisiae were isolated from alpha * cells having the a/alpha aar1-6 genotype (exhibiting alpha mating ability and weak a mating ability as a result of a defect in a1-alpha 2 repression). Among these sterile mutants, we found two ste5 mutants together with putative ste7, ste11, and ste12 mutants of the signal transduction pathway of mating pheromones. The amino acid sequence of the Ste5p protein predicted from the nucleotide sequence of a cloned STE5 DNA has a domain rich in acidic amino acids close to its C terminus, a cysteine-rich sequence, resembling part of a zinc finger structure, in its N-terminal half, and a possible target site of cyclic AMP-dependent protein kinase at its C terminus. Northern (RNA) blot analysis revealed that STE5 transcription is under a1-alpha 2-Aar1p repression. The MAT alpha 1 cistron has a single copy of the pheromone response element in its 5' upstream region, and its basal level of transcription was reduced in these ste mutant cells. However, expression of the MAT alpha 1 cistron was not enhanced appreciably by pheromone signals. One of the ste5 mutant alleles conferred a sterile phenotype to a/alpha aar1-6 cells but a mating ability to MATa cells.

Function of the ste signal transduction pathway for mating pheromones sustains MAT alpha 1 transcription in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (4) ◽  
pp. 2050-2060
Author(s):  
Y Mukai ◽  
S Harashima ◽  
Y Oshima
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Single Copy ◽  
Upstream Region ◽  
Transduction Pathway ◽  
Mating Ability ◽  
Mating Pheromones ◽  
C Terminus ◽  
Dependent Protein

Sterile mutants of Saccharomyces cerevisiae were isolated from alpha * cells having the a/alpha aar1-6 genotype (exhibiting alpha mating ability and weak a mating ability as a result of a defect in a1-alpha 2 repression). Among these sterile mutants, we found two ste5 mutants together with putative ste7, ste11, and ste12 mutants of the signal transduction pathway of mating pheromones. The amino acid sequence of the Ste5p protein predicted from the nucleotide sequence of a cloned STE5 DNA has a domain rich in acidic amino acids close to its C terminus, a cysteine-rich sequence, resembling part of a zinc finger structure, in its N-terminal half, and a possible target site of cyclic AMP-dependent protein kinase at its C terminus. Northern (RNA) blot analysis revealed that STE5 transcription is under a1-alpha 2-Aar1p repression. The MAT alpha 1 cistron has a single copy of the pheromone response element in its 5' upstream region, and its basal level of transcription was reduced in these ste mutant cells. However, expression of the MAT alpha 1 cistron was not enhanced appreciably by pheromone signals. One of the ste5 mutant alleles conferred a sterile phenotype to a/alpha aar1-6 cells but a mating ability to MATa cells.

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