Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C

2004 ◽  
Vol 121 (2) ◽  
pp. 276
Author(s):  
B.M. Tsai ◽  
M. Wang ◽  
J.M. Pitcher ◽  
D.R. Meldrum
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Cytokine Expression ◽  
Pulmonary Vasoconstriction ◽  
Kinase C ◽  
Artery Tissue

Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C

2004 ◽  
Vol 287 (6) ◽  
pp. L1215-L1219 ◽  
Author(s):  
Ben M. Tsai ◽  
Meijing Wang ◽  
Jeffrey M. Pitcher ◽  
Kirstan K. Meldrum ◽  
Daniel R. Meldrum
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Pulmonary Vasoconstriction ◽  
Kinase C ◽  
Tnf Α ◽  
Artery Tissue ◽  
Pkc Activation

Pulmonary arteries exhibit a marked vasoconstriction when exposed to hypoxic conditions. Although this may be an adaptive response to match lung ventilation with perfusion, the potential consequences of sustained pulmonary vasoconstriction include pulmonary hypertension and right heart failure. Concomitant production of proinflammatory mediators during hypoxia may exacerbate acute increases in pulmonary vascular resistance. We hypothesized that acute hypoxia causes pulmonary arterial contraction and increases the pulmonary artery tissue expression of proinflammatory cytokines via a protein kinase C (PKC)-mediated mechanism. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings during hypoxia in the presence and absence of the PKC inhibitors calphostin C or chelerythrine. In separate experiments, pulmonary artery rings were treated with the PKC activator thymeleatoxin for 60 min. After hypoxia, with or without PKC inhibition, or PKC activation alone, pulmonary artery rings were subjected to mRNA analysis for TNF-α and IL-1β via RT-PCR. Our results showed that, in isolated pulmonary arteries, hypoxia caused a biphasic contraction and increased expression of TNF-α and IL-1β mRNA. Both effects were inhibited by PKC inhibition. PKC activation resulted in pulmonary artery contraction and increased the pulmonary artery expression of TNF-α and IL-1β mRNA. These findings suggest that hypoxia induces the expression of inflammatory cytokines and causes vasoconstriction via a PKC-dependent mechanism. We conclude that PKC may have a central role in modulating hypoxic pulmonary vasoconstriction, and further elucidation of its involvement may lead to therapeutic application.

Role of protein kinase C in 15-HETE-induced hypoxic pulmonary vasoconstriction

2009 ◽  
Vol 80 (2-3) ◽  
pp. 115-123 ◽  
Author(s):  
Lei Guo ◽  
Xiaobo Tang ◽  
Xiaojie Chu ◽  
Lihua Sun ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasoconstriction ◽  
Kinase C

Tumor necrosis factor-alpha activates pulmonary artery endothelial protein kinase C

1993 ◽  
Vol 264 (1) ◽  
pp. L7-L14 ◽  
Author(s):  
T. J. Ferro ◽  
D. M. Parker ◽  
L. M. Commins ◽  
P. G. Phillips ◽  
A. Johnson
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Pulmonary Artery ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Kinase C ◽  
Factor Alpha ◽  
Necrosis Factor

We investigated the hypothesis that tumor necrosis factor-alpha (TNF) activates pulmonary endothelial protein kinase C (PKC). Confluent bovine pulmonary artery endothelial monolayers were exposed to recombinant human TNF, and the translocation of PKC, an indicator of enzyme activation, was studied using both slot immunoblotting and immunofluorescence. For slot immunoblot analysis, membrane and cytosol lysate fractions were prepared, and PKC antigen was assessed using MC5 monoclonal anti-PKC antibody. TNF (1,000 U/ml for 15 min) induced translocation of PKC into the membrane. Immunofluorescence analysis with the MC5 antibody was also used. Monolayers treated with culture medium showed diffuse cytoplasmic fluorescence. In contrast, treatment with either TNF (1,000 U/ml for 15 min) or 1,2-dioctanoylglycerol (4 x 10(-5) M for 5 min), a diacylglycerol that activates PKC, resulted in translocation of fluorescence to the cell periphery; fine, punctate PKC-associated fluorescence was localized to the margins of cells. The TNF-induced translocation of PKC was inhibited using either IP-300 polyclonal anti-TNF antibody (indicating that the TNF effect was not due to the vehicle or contaminating endotoxin) or calphostin C (10(-6) M for 15 min), which inhibits PKC activation by interacting with the regulatory diacylglycerol-binding domain. TNF treatment had no effect on either the content of PKC, or of total protein, in the membrane + cytosol, and cycloheximide (40 microM for 5 min) did not alter the translocation of PKC induced by TNF; these results indicate that the effect of TNF on PKC translocation was related to neither de novo membrane synthesis of PKC (as opposed to translocation per se) nor nonspecific augmentation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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