The kinase inhibitor iso-H7 stimulates rat satellite cell differentiation through a non-protein kinase C pathway by increasing myogenin expression level

1996 ◽  
Vol 12 (3) ◽  
pp. 177-185 ◽  
Author(s):  
C. Lagord ◽  
M.-P. Leibovitch ◽  
G. Carpentier ◽  
S.-A. Leibovitch ◽  
I. Martelly
Keyword(s):  
Protein Kinase C ◽  
Cell Differentiation ◽  
Protein Kinase ◽  
Satellite Cell ◽  
Kinase Inhibitor ◽  
Expression Level ◽  
Kinase C

Role of protein kinase C in T-cell antigen receptor regulation of p21ras: evidence that two p21ras regulatory pathways coexist in T cells

1992 ◽  
Vol 12 (7) ◽  
pp. 3305-3312
Author(s):  
M Izquierdo ◽  
J Downward ◽  
J D Graves ◽  
D A Cantrell
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Antigen Receptor ◽  
Permeabilized Cell ◽  
Regulatory Pathways ◽  
Kinase C ◽  
Stimulation Of

T-lymphocyte activation via the antigen receptor complex (TCR) results in accumulation of p21ras in the active GTP-bound state. Stimulation of protein kinase C (PKC) can also activate p21ras, and it has been proposed that the TCR effect on p21ras occurs as a consequence of TCR regulation of PKC. To test the role of PKC in TCR regulation of p21ras, a permeabilized cell system was used to examine TCR regulation of p21ras under conditions in which TCR activation of PKC was blocked, first by using a PKC pseudosubstrate peptide inhibitor and second by using ionic conditions that prevent phosphatidyl inositol hydrolysis and hence diacylglycerol production and PKC stimulation. The data show that TCR-induced p21ras activation is not mediated exclusively by PKC. Thus, in the absence of PKC stimulation, the TCR was still able to induce accumulation of p21ras-GTP complexes, and this stimulation correlated with an inactivation of p21ras GTPase-activating proteins. The protein tyrosine kinase inhibitor herbimycin could prevent the non-PKC-mediated, TCR-induced stimulation of p21ras. These data indicate that two mechanisms for p21ras regulation coexist in T cells: one PKC mediated and one not. The TCR can apparently couple to p21ras via a non-PKC-controlled route that may involve tyrosine kinases.

The protein kinase C inhibitor H-7 activates human neutrophils: effect on shape, actin polymerization, fluid pinocytosis and locomotion

1990 ◽  
Vol 96 (1) ◽  
pp. 99-106
Author(s):  
H.U. Keller ◽  
V. Niggli ◽  
A. Zimmermann ◽  
R. Portmann
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Actin Polymerization ◽  
Kinase Inhibitor ◽  
Human Neutrophils ◽  
Kinase C ◽  
Chemotactic Peptides ◽  
Protein Kinase C Inhibitor ◽  
Shape Changes ◽  
Stimulation Of

The present study demonstrates new properties of H-7. The protein kinase inhibitor H-7 is a potent activator of several neutrophil functions. Stimulation of initially spherical nonmotile neutrophils elicits vigorous shape changes within a few seconds, increases in cytoskeletal actin, altered F-actin distribution, increased adhesiveness and a relatively small increase in pinocytic activity. H-7 has also chemokinetic activities. Depending on the experimental condition, H-7 may elicit or inhibit neutrophil locomotion. It failed to induce chemotaxis. Thus, the response pattern elicited by H-7 is different from that of other leukocyte activators such as chemotactic peptides, PMA or diacylglycerols. The finding that H-7 can elicit shape changes, actin polymerization and pinocytosis suggests that these events can occur without activation of protein kinase C (PKC). PMA-induced shape changes and stimulation of pinocytosis were not inhibited by H-7.

TNF-α and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms

2001 ◽  
Vol 281 (6) ◽  
pp. G1405-G1412 ◽  
Author(s):  
T. Suzuki ◽  
E. Grand ◽  
C. Bowman ◽  
J. L. Merchant ◽  
A. Todisco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Interleukin 1 ◽  
Mitogen Activated Protein Kinase ◽  
G Cells ◽  
Kinase C ◽  
Tnf Α ◽  
Mitogen Activated Protein

Helicobacter pyloriand proinflammatory cytokines have a direct stimulatory effect on gastrin release from isolated G cells, but little is known about the mechanism by which these factors regulate gastrin gene expression. We explored whether tumor necrosis factor (TNF)-α and interleukin (IL)-1 directly regulate gastrin gene expression and, if so, by what mechanism. TNF-α and IL-1 significantly increased gastrin mRNA in canine G cells to 181 ± 18% and 187 ± 28% of control, respectively, after 24 h of treatment. TNF-α and IL-1 stimulated gastrin promoter activity to a maximal level of 285 ± 12% and 415 ± 26% of control. PD-98059 (a mitogen-activated protein kinase kinase inhibitor), SB-202190 (a p38 kinase inhibitor), and GF-109203 (a protein kinase C inhibitor) inhibited the stimulatory action of both cytokines on the gastrin promoter. In conclusion, both cytokines can directly regulate gastrin gene expression via a mitogen-activated protein kinase- and protein kinase C-dependent mechanism. These data suggest that TNF-α and IL-1 may play a direct role in Helicobacter pylori-induced hypergastrinemia.

scholarly journals Triggering of Suicidal Erythrocyte Death by Zosuquidar

2015 ◽  
Vol 37 (6) ◽  
pp. 2355-2365 ◽  
Author(s):  
Marilena Briglia ◽  
Antonella Fazio ◽  
Caterina Faggio ◽  
Florian Lang
Keyword(s):  
Cell Death ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Annexin V ◽  
Tumor Cell Death ◽  
P38 Kinase ◽  
Forward Scatter ◽  
Kinase C ◽  
Erythrocyte Surface

Background: The P-glycoprotein inhibitor zosuquidar (LY335979) is clinically used to augment the effect of cytostatic drugs on suicidal tumor cell death or apoptosis. The present study explored whether the substance is cytotoxic to erythrocytes. Upon injury, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i), oxidative stress and activation of several kinases, such as p38 kinase and protein kinase C. Methods: Phosphatidylserine abundance at the erythrocyte surface was quantified from binding of FITC-labelled annexin-V, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. Results: A 48 h treatment of human erythrocytes with zosuquidar significantly increased the percentage of annexin-V-binding cells (2 and 4 µg/ml), significantly decreased forward scatter (4 µg/ml), significantly increased [Ca2+]i (4 µg/ml), but did not significantly modify ROS. The up-regulation of annexin-V-binding following zosuquidar (4 µg/ml) treatment was significantly blunted by removal of extracellular Ca2+, by presence of p38 kinase inhibitor SB203580 (2 µM) and by presence of protein kinase C inhibitor calphostin (100 nM). Conclusions: Exposure of erythrocytes to zosuquidar triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect involving Ca2+ entry and requiring activity of SB203580 and calphostin sensitive kinases.

d-Glucose and insulin stimulate migration and tubular formation of human endothelial cells in vitro

1999 ◽  
Vol 277 (3) ◽  
pp. E433-E438 ◽  
Author(s):  
Satoshi Shigematsu ◽  
Keishi Yamauchi ◽  
Kohji Nakajima ◽  
Sachiko Iijima ◽  
Toru Aizawa ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Endothelial Cell Migration ◽  
Insulin Effect ◽  
Kinase C ◽  
Tubular Formation ◽  
Stimulation Of

Effects of highd-glucose and insulin on the endothelial cell migration and tubular formation were investigated with the use of ECV304 cells, a clonal human umbilical cord endothelial cell line. Exposure of the cells to highd-glucose resulted in a marked increase in the migration, which was blocked by inhibitors of protein kinase C such as H7 (10 μM) and GF109203X (200 nM). Furthermore, a protein kinase C agonist, phorbol 12-myristate 13-acetate, had an effect similar to that of glucose on ECV304 cells. Glucose stimulation of the migration was additively enhanced by 100 nM insulin, and the insulin effect was found to be unaffected by either PD-98059 or wortmannin, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase inhibitor and a phosphatidylinositol 3-kinase inhibitor, respectively. Neither did H7 inhibit insulin stimulation of the migration. In contrast, a combination of high d-glucose and insulin, rather than either one alone, promoted tubular formation, which was inhibited by addition of 10 μM PD-98059. Stimulation of ECV304 cells by the combination of highd-glucose and insulin also caused an activation of MAPK, which was again obliterated by the same concentration of PD-98059. In conclusion, human endothelial cell migration and tubular formation are stimulated by highd-glucose and insulin in different ways. In the former reaction, either is effective, a combination of the two results in an additive effect, and activation of protein kinase C is involved. In contrast, tubular formation will only occur in the presence of a combination of highd-glucose and insulin, and MAPK plays an essential role.

scholarly journals The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase

2002 ◽  
Vol 11 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Pravit Akarasereenont ◽  
Kitirat Techatraisak ◽  
Athiwat Thaworn ◽  
Sirikul Chotewuttakorn
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenase (COX), existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF) has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC). The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX2 was assessed by measuring the production of 6-keto-prostaglandin F1α in the presence of exogenous arachidonic acids (10 μM, 10 min) by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml), COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml) was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 μg/ml), but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml). Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role.

Relaxin stimulates atrial natriuretic peptide secretion in perfused rat heart

1996 ◽  
Vol 150 (3) ◽  
pp. 487-495 ◽  
Author(s):  
M Toth ◽  
P Taskinen ◽  
H Ruskoaho
Keyword(s):  
Heart Rate ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Rat Heart ◽  
Perfusion Pressure ◽  
Kinase Inhibitor ◽  
Dependent Protein Kinase ◽  
Kinase C ◽  
Dependent Protein ◽  
Heart Preparation

Abstract Relaxin, a reproductive hormone of the insulin-like growth factor family, increases heart rate in experimental animals but its other actions on cardiac function and cellular mechanisms responsible for the positive chronotrophic effect remain unknown. We have studied the actions of human recombinant gene-2 relaxin on the release of atrial natriuretic peptide (ANP) and cardiac function (heart rate, contractile force, perfusion pressure) as well as the underlying signal transduction mechanisms by using the isolated perfused spontaneously beating rat heart preparation. The administration of relaxin into the perfusion fluid at concentrations of 1·5, 3 or 10 nm for 30 min caused a dose-dependent sustained increase in heart rate, while contractile force and perfusion pressure remained unchanged. In addition, infusion of relaxin at a concentration of 10 nm into the perfusate produced a gradual 1·5-fold increase in immunoreactive ANP (IR-ANP) secretion (from 456 ± 76 to 701 ± 124 pg/ml, F=4·5, P<0·001). The ANP secretory and chronotrophic effects of relaxin appear to involve the activation of protein kinase C, since administration of a protein kinase C inhibitor staurosporine at a concentration of 30 nm completely blocked the effect of relaxin (10 nm) on IR-ANP secretion P<0·001) and heart rate (P<0·001). A cAMP-dependent protein kinase inhibitor, H-89 (100 nm), also substantially reduced the ANP secretory effect of relaxin and attenuated the increase in heart rate during the sustained phase of the relaxin infusion (P<0·001). KN-62 (3 μm), a Ca2+/calmodulin-dependent protein kinase inhibitor, decreased the positive chronotrophic effect of relaxin (P<0·001) but did not influence significantly the effect of relaxin on IR-ANP release in isolated perfused rat heart preparation. These results provide the first evidence that relaxin stimulates the secretion of ANP from isolated perfused rat hearts. Our results also suggest that relaxin modulates ANP secretion by activation of protein kinase C and cAMP-dependent protein kinase pathways. Journal of Endocrinology (1996) 150, 487–495

Sign in / Sign up

Export Citation Format

Share Document