scholarly journals cAMP-dependent protein kinase activation inhibits proliferation and enhances apoptotic effect of tumor necrosis factor-α in NCI-H295R adrenocortical cells

2004 ◽  
Vol 33 (2) ◽  
pp. 511-522 ◽  
Author(s):  
J Liu ◽  
X-D Li ◽  
A Ora ◽  
P Heikkilä ◽  
A Vaheri ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Adrenocortical Cell ◽  
Dependent Protein Kinase ◽  
Kinase Activation ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
H295r Cells ◽  
Induced Apoptosis ◽  
Factor Α

Adrenocorticotropin is the major regulator of adrenocortical development and function. It acts mainly through the cAMP-dependent protein kinase A (PKA) pathway. Our aim was to study the interaction of tumor necrosis factor-α (TNFα) and the PKA pathway in adrenocortical cell proliferation and apoptosis. The PKA activator Dibutyryl cAMP ((Bu)2cAMP) strongly induced differentiation and inhibited proliferation in the human adrenocortical cell line NCI-H295R (H295R). TNFα induced apoptosis of H295R cells. Interestingly, (Bu)2cAMP treatment clearly enhanced TNFα-induced apoptosis in H295R cells, but not in another human adrenocortical cell line SW-13, the mouse adrenocortical Y-1 cell line or the human HeLa cell line. This synergistic effect was not due to the (Bu)2cAMP-induced glucocorticoid secretion since dexamethasone had no significant effect on the TNFα-induced apoptosis. (Bu)2cAMP treatment rapidly increased the expression of the proto-oncogene c-myc in H295R cells, but not in SW-13, Y-1 or HeLa cells. In transient c-myc transfection assay, c-myc expression associated with decreased expression of the proliferation marker Ki-67 in H295R cells. In conclusion, cAMP-dependent protein kinase activation reduced proliferation and augmented TNFα-induced apoptosis in adrenocortical H295R cells, and these effects were associated with increased c-myc expression.

cAMP-dependent protein kinase regulates renal epithelial cell properties

1991 ◽  
Vol 260 (6) ◽  
pp. C1290-C1299 ◽  
Author(s):  
K. Amsler ◽  
S. Ghatani ◽  
B. A. Hemmings
Keyword(s):  
Protein Kinase ◽  
Epithelial Cell ◽  
Cell Line ◽  
Cell Junctions ◽  
Kinetic Properties ◽  
Wild Type ◽  
Dependent Protein Kinase ◽  
Renal Epithelial Cell ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein

Previous studies have implicated adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) in regulation of both growth and expression of differentiated function in the pig renal epithelial cell, LLC-PK1. To investigate this possible regulatory mechanism, we compared growth behavior, morphology, and appearance of two differentiated functions, Na-hexose symport (SYMP) and gamma-glutamyl transpeptidase (gamma-GT), in the LLC-PK1 line and two PKA-deficient mutants (FIB4 and FIB6). Compared with the wild-type cell line, the mutant lines continued to proliferate at higher population densities and exhibited altered cell morphology, poorer formation of the brush-border structure, and decreased or lack of expression of SYMP and gamma-GT activities. Wild-type and mutant cells exhibit an identical logarithmic growth rate. Both lines form cell-cell junctions and exhibit identical kinetic properties of expressed SYMP activity. These results strongly support the hypothesis that PKA modulates a defined subset of cellular processes, including aspects of growth control and expression of the differentiated phenotype, in this renal epithelial cell line.

Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase

1978 ◽  
Vol 234 (4) ◽  
pp. H432-H438
Author(s):  
S. L. Keely ◽  
T. M. Lincoln ◽  
J. D. Corbin
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Inhibitory Effect ◽  
Contractile Force ◽  
Protein Kinase Activity ◽  
Dependent Protein Kinase ◽  
Kinase Activation ◽  
Camp Dependent Protein Kinase ◽  
Cholinergic Agent ◽  
Dependent Protein

In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (cGMP) levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. The data suggest that changes in cAMP-dependent protein kinase activity can explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force.

scholarly journals Characterization of cAMP-dependent protein kinase activation by CCK in rat pancreas

FEBS Letters ◽  
1993 ◽  
Vol 316 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Christopher R. Marino ◽  
Steven D. Leach ◽  
Jean F. Schaefer ◽  
Laurence J. Miller ◽  
Fred S. Gorelick
Keyword(s):  
Protein Kinase ◽  
Dependent Protein Kinase ◽  
Kinase Activation ◽  
Rat Pancreas ◽  
Camp Dependent Protein Kinase ◽  
Protein Kinase Activation ◽  
Dependent Protein

scholarly journals Estrogen-Induced Apoptosis of Breast Epithelial Cells Is Blocked by NO/cGMP and Mediated by Extranuclear Estrogen Receptors

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5602-5616 ◽  
Author(s):  
Irida Kastrati ◽  
Praneeth D. Edirisinghe ◽  
Gihani T. Wijewickrama ◽  
Gregory R. J. Thatcher
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Estrogen Receptors ◽  
Cell Line ◽  
Mammary Epithelial ◽  
Dependent Protein Kinase ◽  
No Donors ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Induced Apoptosis

Estrogen action, via both nuclear and extranuclear estrogen receptors (ERs), induces a variety of cellular signals that are prosurvival or proliferative, whereas nitric oxide (NO) can inhibit apoptosis via caspase S-nitrosylation and via activation of soluble guanylyl cyclase to produce cGMP. The action of 17β-estradiol (E2) at ER is known to elicit NO signaling via activation of NO synthase (NOS) in many tissues. The MCF-10A nontumorigenic, mammary epithelial cell line is genetically stable and insensitive to estrogenic proliferation. In this cell line, estrogens or NOS inhibitors alone had no significant effect, whereas in combination, apoptosis was induced rapidly in the absence of serum; the presence of inducible NOS was confirmed by proteomic analysis. The application of pharmacological agents determined that apoptosis was dependent upon NO/cGMP signaling via cyclic GMP (cGMP)-dependent protein kinase and could be replicated by inhibition of the phosphatidylinositol 3 kinase/serine-threonine kinase pathway prior to addition of E2. Apoptosis was confirmed by nuclear staining and increased caspase-3 activity in E2 + NOS inhibitor-treated cells. Apoptosis was partially inhibited by a pure ER antagonist and replicated by agonists selective for extranuclear ER. Cells were rescued from E2-induced apoptosis after NOS blockade, by NO-donors and cGMP pathway agonists; preincubation with NO donors was required. The NOS and ER status of breast cancer tissues is significant in etiology, prognosis, and therapy. In this study, apoptosis of preneoplastic mammary epithelial cells was triggered by estrogens via a rapid, extranuclear ER-mediated response, after removal of an antiapoptotic NO/cGMP/cGMP-dependent protein kinase signal.

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