Oxidant and angiotensin II-induced subcellular translocation of protein kinase C in pulmonary artery endothelial cells

1992 ◽  
Vol 7 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Jawaharalal M. Patel ◽  
K. Madhavi Sekharam ◽  
Edward R. Block
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Kinase C ◽  
Subcellular Translocation

scholarly journals Serine Phosphorylation Sites on IRS2 Activated by Angiotensin II and Protein Kinase C To Induce Selective Insulin Resistance in Endothelial Cells

2013 ◽  
Vol 33 (16) ◽  
pp. 3227-3241 ◽  
Author(s):  
Kyoungmin Park ◽  
Qian Li ◽  
Christian Rask-Madsen ◽  
Akira Mima ◽  
Koji Mizutani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Tyrosine Phosphorylation ◽  
Mutational Analysis ◽  
Dominant Negative ◽  
Serine Phosphorylation ◽  
Kinase C ◽  
Pkc Activation

Protein kinase C (PKC) activation, induced by hyperglycemia and angiotensin II (AngII), inhibited insulin-induced phosphorylation of Akt/endothelial nitric oxide (eNOS) by decreasing tyrosine phosphorylation of IRS2 (p-Tyr-IRS2) in endothelial cells. PKC activation by phorbol ester (phorbol myristate acetate [PMA]) reduced insulin-induced p-Tyr-IRS2 by 46% ± 13% and, similarly, phosphorylation of Akt/eNOS. Site-specific mutational analysis showed that PMA increased serine phosphorylation at three sites on IRS2 (positions 303, 343, and 675), which affected insulin-induced tyrosine phosphorylation of IRS2 at positions 653, 671, and 911 (p-Tyr-IRS2) and p-Akt/eNOS. Specific PKCβ2 activation decreased p-Tyr-IRS2 and increased the phosphorylation of two serines (Ser303 and Ser675) on IRS2 that were confirmed in cells overexpressing single point mutants of IRS2 (S303A or S675A) containing a PKCβ2-dominant negative or selective PKCβ inhibitor. AngII induced phosphorylation only on Ser303 of IRS2 and inhibited insulin-induced p-Tyr911 of IRS2 and p-Akt/eNOS, which were blocked by an antagonist of AngII receptor I, losartan, or overexpression of single mutant S303A of IRS2. Increases in p-Ser303 and p-Ser675 and decreases in p-Tyr911 of IRS2 were observed in vessels of insulin-resistant Zucker fatty rats versus lean rats. Thus, AngII or PKCβ activation can phosphorylate Ser303 and Ser675 in IRS2 to inhibit insulin-induced p-Tyr911 and its anti-atherogenic actions (p-Akt/eNOS) in endothelial cells.

scholarly journals Mechanisms regulating cAMP-mediated growth of bovine neonatal pulmonary artery smooth muscle cells

1999 ◽  
Vol 276 (6) ◽  
pp. L1010-L1017 ◽  
Author(s):  
Alexandra Guldemeester ◽  
Kurt R. Stenmark ◽  
George H. Brough ◽  
Troy Stevens
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Growth Responses ◽  
Camp Content ◽  
Kinase C ◽  
Pulmonary Artery Smooth Muscle ◽  
Stimulation Of

Neonatal pulmonary artery smooth muscle cells (PASMCs) exhibit enhanced growth capacity and increased growth responses to mitogenic stimuli compared with adult PASMCs. Because intracellular signals mediating enhanced growth responses in neonatal PASMCs are incompletely understood, we questioned whether 1) Gq agonists increase cAMP content and 2) increased cAMP is proproliferative. Endothelin-1 and angiotensin II increased both cAMP content and proliferation in neonatal but not in adult PASMCs. Inhibition of protein kinase C and protein kinase A activity nearly eliminated the endothelin-1- and angiotensin II-induced growth of neonatal PASMCs. Moreover, cAMP increased proliferation in neonatal but not in adult cells. Protein kinase C-stimulated adenylyl cyclase was expressed in both cell types, suggesting that insensitivity to stimulation of cAMP in adult cells was not due to decreased enzyme expression. Our data collectively indicate that protein kinase C stimulation of cAMP is a critical signal mediating proliferation of neonatal PASMCs that is absent in adult PASMCs and therefore may contribute to the unique proproliferative phenotype of these neonatal cells.

Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells

2001 ◽  
Vol 281 (2) ◽  
pp. L403-L411 ◽  
Author(s):  
Sang-Do Lee ◽  
Dong-Soon Lee ◽  
Yong-Gam Chun ◽  
Tae-Sun Shim ◽  
Chae-Man Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Cigarette Smoke ◽  
De Novo ◽  
Ex Vivo ◽  
Cigarette Smoke Extract ◽  
Kinase C

We examined the mechanism of endothelin (ET)-1 regulation by cigarette smoke extract (CSE) and the effect of platelets on CSE-induced stimulation of ET-1 gene expression in human and bovine pulmonary artery endothelial cells (PAECs). Our data show that CSE (1%) induces ET-1 gene expression (after 1 h) and ET-1 peptide synthesis (after 4 h) in bovine PAECs. The induction of preproET-1 mRNA level was due to de novo transcription, and new protein synthesis was not required for this induction. The protein kinase C inhibitors staurosporine (10−8mol/l) and calphostin C (10−7mol/l) abolished the induction of ET-1 gene expression by CSE in bovine and human PAECs. Although a lower concentration of platelets (106cells/ml in bovine PAECs; 107cells/ml in human PAECs) did not significantly alter ET-1 gene expression in PAECs, incubation of platelets with CSE (1%) and PAECs produced a significant increase in preproET-1 mRNA and ET-1 peptide compared with the values in the presence of CSE (1%) alone. CSE (1%) induced platelet aggregation and increased the expression of platelet membrane glycoproteins ex vivo. Thus our data suggest that CSE stimulates ET-1 gene expression via PKC in PAECs. CSE and platelets showed a synergistic effect on ET-1 gene expression, possibly through the activation of platelets by CSE.

Influence of vasoactive agents on cytoplasmic free calcium in vascular endothelial cells

1988 ◽  
Vol 65 (5) ◽  
pp. 2221-2227 ◽  
Author(s):  
U. S. Ryan ◽  
P. V. Avdonin ◽  
E. Y. Posin ◽  
E. G. Popov ◽  
S. M. Danilov ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Platelet Activating Factor ◽  
Free Calcium ◽  
Kinase C ◽  
Cytoplasmic Free Calcium

The regulation of cytoplasmic free calcium concentration [( Ca2+]i) in endothelial cells (EC) derived from human umbilical vein, aorta, and pulmonary artery, or from bovine pulmonary artery, was studied by means of the fluorescent Ca2+ indicator indo-1. Histamine and thrombin caused a rapid transient elevation in [Ca2+]i in the EC of all the human blood vessels tested. In aortic EC, [Ca2+]i also rose in response to ATP and bradykinin. It was shown that in bovine pulmonary artery EC [Ca2+]i rises in response to platelet-activating factor (PAF) and thrombin. For a more detailed investigation of the receptor-mediated mechanism of [Ca2+]i increase in EC we used histamine as a stimulating agent. Histamine effects were seen at concentrations ranging from 5 X 10(-7) to 10(-4) M [50% effective dose (ED50) approximately 2-4 microM)] and were mediated by H1-receptors. The histamine-induced increase in [Ca2+]i was not markedly diminished when the extracellular calcium was bound by excess ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The data obtained indicate that the histamine effect is best explained by Ca2+ mobilization from intracellular stores. The histamine-induced increase in [Ca2+]i was not influenced by elevating the intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or cyclic guanylic acid (cGMP) by use of isobutylmethylxanthine and forskolin or by nitroprusside preincubation, respectively. However, the protein kinase C stimulator, phorbol myristate acetate (PMA), strongly inhibits [Ca2+]i elevation. It is assumed that a negative feedback mechanism that blocks receptor-mediated [Ca2+]i increase is triggered as a result of the activation of protein kinase C.

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