Hypertrophic growth of cultured neonatal rat heart cells mediated by type 1 angiotensin II receptor

1994 ◽  
Vol 266 (6) ◽  
pp. H2443-H2451 ◽  
Author(s):  
S. Miyata ◽  
T. Haneda
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Hypertrophic Growth ◽  
Kinase C

Primary cultures of neonatal cardiac myocytes were used to determine the identity of second messengers that are involved in angiotensin II (ANG II) receptor-mediated effects on cardiac hypertrophy and the type of ANG II receptor that is involved in ANG II-induced cell growth. Treatment of myocytes with ANG II significantly increased the protein-to-DNA and the RNA-to-DNA ratios. ANG II accelerated rates of protein synthesis by 24.9%. Intracellular free calcium was transiently increased after ANG II exposure. The activity of protein kinase C in particulate fractions was transiently increased after exposure to ANG II but returned to control level. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to ANG II. After ANG II treatment, the content of c-Fos mRNA was increased. The stimulatory effects of ANG II on these parameters were inhibited by the type 1 angiotensin II receptor (AT1) antagonist, losartan. These studies demonstrate that ANG II-induced hypertrophic growth is, at least in part, mediated through AT1 receptors.

Angiotensin II Induces Translocation of Protein Kinase C α and ε in Neonatal Rat Cardiac Myocytes

2001 ◽  
Vol 7 (S2) ◽  
pp. 1016-1017
Author(s):  
Tara A. Bullard ◽  
Edie Goldsmith ◽  
Robert L. Price
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Heart Development ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Kinase C ◽  
Transduction Mechanisms

Angiotensin II (Ang II) plays an important role in heart development and has been shown to stimulate the formation of premyofibrils and differentiation of cardiac myocytes. Ang II signaling occurs through two types of receptors, the AT1 and AT2 receptors, both of which appear to play a role in the development of the myocardium. Through the use of specific Ang II receptor blockers it as been shown that blocking the AT1 receptor with Losartan (Merck) inhibits the formation of premyofibrils and sarcomere formation and that blocking the AT2 receptor with PD123,319 (Parke-Davis) inhibits the formation of trabeculae in the developing heart.In a number of cases it has been shown that signal transduction mechanisms operate through different growth factor receptors and elicit specific responses within a cell type. Protein kinase C (PKC) is a family of closely related signal transduction enzymes that phosphorylate proteins on serine or threonine residues.

scholarly journals Rate of calcium entry determines the rapid changes in protein kinase C activity in angiotensin II-stimulated adrenal glomerulosa cells

1994 ◽  
Vol 297 (3) ◽  
pp. 523-528 ◽  
Author(s):  
I Kojima ◽  
N Kawamura ◽  
H Shibata
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Specific Substrate ◽  
Ang Ii ◽  
Kinase C ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Peptide Phosphorylation

The present study was conducted to monitor precisely the activity of protein kinase C (PKC) in adrenal glomerulosa cells stimulated by angiotensin II (ANG II). PKC activity in cells was monitored by measuring phosphorylation of a synthetic KRTLRR peptide, a specific substrate for PKC, immediately after the permeabilization of the cells with digitonin [Heasley and Johnson J. Biol. Chem. (1989) 264, 8646-8652]. Addition of 1 nM ANG II induced a gradual increase in KRTLRR peptide phosphorylation, which reached a peak at 30 min, and phosphorylation was sustained thereafter. When the action of ANG II was terminated by adding [Sar1,Ala8]ANG II, a competitive antagonist, both Ca2+ entry and KRTLRR phosphorylation ceased rapidly, whereas diacylglyercol (DAG) content was not changed significantly within 10 min. Similarly, when blockade of Ca2+ entry was achieved by decreasing extracellular Ca2+ to 1 microM or by adding 1 microM nitrendipine, KRTLRR peptide phosphorylation was decreased within 5 min. In addition, restoration of Ca2+ entry was accompanied by an immediate increase in KRTLRR peptide phosphorylation. Under the same condition, DAG content did not change significantly. We then examined the role of the PKC pathway in ANG II-induced aldosterone production. Ro 31-8220 inhibited ANG II-induced KRTLRR phosphorylation without affecting the activity of calmodulin-dependent protein kinase II. In the presence of Ro 31-8220, ANG II-mediated aldosterone production was decreased to approx. 50%. Likewise, intracellular administration of PKC19-36, a sequence corresponding to residues 19-36 of the regulatory domain of PKC known to inhibit PKC activity, attenuated ANG II-mediated activation of PKC and aldosterone output. These results indicate a critical role of Ca2+ entry in the regulation of PKC activity by ANG II.

Regulation of vascular angiotensin II receptors by EGF

1997 ◽  
Vol 273 (4) ◽  
pp. C1241-C1249 ◽  
Author(s):  
Michael E. Ullian ◽  
John R. Raymond ◽  
Mark C. Willingham ◽  
Richard V. Paul
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Protein Kinase ◽  
Pertussis Toxin ◽  
Receptor Expression ◽  
Ang Ii ◽  
Receptor Density ◽  
Kinase C ◽  
Surface Receptor

After vascular endothelial injury, angiotensin II (ANG II) plays a role in the resulting hypertrophic response, and expression of epidermal growth factor (EGF) is enhanced. Therefore, we tested the possibility that EGF regulates vascular ANG II action and receptor expression. Incubation of cultured aortic vascular smooth muscle cells (VSMC) with EGF (or basic fibroblast growth factor but not platelet-derived growth factor isoforms) resulted in concentration-dependent (1–50 ng/ml EGF), time-dependent (>8 h), and reversible decreases in ANG II surface receptor density. For example, a 50% reduction was observed after exposure to 50 ng/ml EGF for 24 h. Incubation of cultured VSMC with 50 ng/ml EGF for 24 h resulted in a 77% reduction in ANG II-stimulated inositol phosphate formation. EGF not only prevented but also reversed ANG II receptor upregulation by 100 nM corticosterone. The specific tyrosine kinase inhibitor tyrphostin A48 (50 μM) reduced EGF-stimulated thymidine incorporation and EGF-stimulated phosphorylation of mitogen-activated protein kinase but did not prevent EGF from reducing ANG II receptor density. Neither pertussis toxin (100 ng/ml) nor downregulation of protein kinase C by phorbol myristate acetate (100 nM for 24 h) prevented EGF from reducing ANG II receptor density. In summary, EGF is a potent negative regulator of vascular ANG II surface receptor density and ANG II action by mechanisms that do not appear to include tyrosine phorphorylation, pertussis toxin-sensitive G proteins, or phorbol ester-sensitive protein kinase C. The possibility that EGF shifts the cell culture phenotype to one that exhibits reduced surface ANG II density cannot be eliminated by the present studies.

Regulation of angiotensin II binding sites in neuronal cultures by protein kinase C

1990 ◽  
Vol 258 (4) ◽  
pp. C610-C617 ◽  
Author(s):  
C. J. Kalberg ◽  
C. Sumners
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Binding Sites ◽  
Phorbol Esters ◽  
Specific Binding ◽  
Neuronal Cultures ◽  
Ang Ii ◽  
Kinase C ◽  
Stimulation Of

The radioligand binding of 125I-angiotensin II (ANG II) and calcium phospholipid-dependent protein kinase C (PKC) activity were measured to study the specificity and mechanisms of PKC involvement in the regulation of ANG II-specific binding site expression in neuronal cultures prepared from the brains of 1-day-old rats. Previously, PKC-activating phorbol esters were shown to increase the specific binding of 125I-ANG II in neuronal cultures. However, phorbol esters have many biological effects, which may nonspecifically act to increase 125I-ANG II-specific binding. In the present study, mezerein and teleocidin A, two activators of PKC that are chemically unrelated to phorbol esters, increased the specific binding of 125I-ANG II in a dose- and time-dependent manner with 50% effective dose (ED50) values of 32 and 79 nM, respectively. The PKC antagonist H-7 dose dependently inhibited phorbol 12-myristate 13-acetate (TPA)-stimulated increases in 125I-ANG II binding, whereas downregulation of PKC activity by chronic phorbol ester incubations of 24 and 48 h prevented TPA-stimulated increases in 125I-ANG II-specific binding. TPA (0.8 microM), mezerein (0.76 microM), and teleocidin A (0.5 microM) all caused a rapid translocation of PKC activity from the cytosol to the particulate fraction by 15 min. Temporally, the maximal stimulation of PKC translocation by mezerein, teleocidin A, and TPA preceded their ability to stimulate maximal 125I-ANG II-specific binding. Taken together, these results suggest that PKC is directly involved in the stimulation of ANG II-specific binding site expression and that translocation of PKC is a prerequisite for the increased expression of ANG II binding sites.

scholarly journals Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1801-1809 ◽  
Author(s):  
Ying Tian ◽  
Roger D. Smith ◽  
Tamas Balla ◽  
Kevin J. Catt
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Time Course ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Glomerulosa Cells

Abstract Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10–50 pm. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

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