scholarly journals Inhibition of phosphatidylinositol 3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis

2000 ◽  
Vol 31 (6) ◽  
pp. 1160-1167 ◽  
Author(s):  
Alliric I. Willis ◽  
Shoichi Fuse ◽  
Xiu Jie Wang ◽  
Emery Chen ◽  
George P. Tuszynski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cell ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase C ◽  
Cell Chemotaxis

Effects of calponin on force generation by single smooth muscle cells

1996 ◽  
Vol 270 (5) ◽  
pp. H1858-H1863 ◽  
Author(s):  
A. Horowitz ◽  
O. Clement-Chomienne ◽  
M. P. Walsh ◽  
T. Tao ◽  
H. Katsuyama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Contractile Force ◽  
Actin Binding ◽  
Aortic Smooth Muscle ◽  
Kinase C ◽  
Protein Kinase C Epsilon

Although the actin-binding and actomyosin adenosinetriphosphatase (ATPase) inhibitory properties of calponin are well documented in vitro, its function in the smooth muscle cell has not been elucidated. To address this question, we utilized the ferret aortic smooth muscle cell, which shows a protein kinase C-dependent contraction even at pCa (-log [Ca2+]) 9.0 in the absence of a change in myosin light chain phosphorylation. Force was recorded from single, briefly permeabilized cells stimulated via a Ca(2+)-independent pathway by either phenylephrine or the epsilon isoenzyme of protein kinase C. Treatment of stimulated cells with wild-type recombinant calponin reduced steady-state contractile force by 45-60%. When calponin application preceded protein kinase C epsilon treatment, contraction was completely suppressed. On the other hand, calponin phosphorylated at Ser175 or mutant calponin with a Ser175 ⇢ Ala replacement had no effect on contractile force. A peptide corresponding to Leu166-Gly194 of calponin, which included an actin-binding domain but excluded the actomyosin ATPase inhibitory region, was synthesized. Treatment of aortic smooth muscle cells with this peptide triggered a concentration-dependent contraction, presumably by alleviating the inhibitory effect of endogenous calponin. A control peptide with a scrambled sequence of the same residues produced no detectable contractile response. Although other interpretations are possible, these results are consistent with the view that calponin participates in thin filament-mediated regulation of smooth muscle contraction and that it may be part of a Ca(2+)-independent pathway downstream of protein kinase C epsilon.

scholarly journals Protein Kinase C Alpha Acting Through Phorbol-12-Myristate 13-Acetate Regulates Nephronectin Gene Expression Via c-Jun and c-Fos Transcription Factors

2021 ◽  
Author(s):  
Mitsuhiro Kinoshita ◽  
Atsushi Yamada ◽  
Kiyohito Sasa ◽  
Kaori Ikezaki ◽  
Tatsuo Shirota ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Small Interfering Rna ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Down Regulation ◽  
Kinase C ◽  
Interfering Rna ◽  
Dose Dependent

Abstract Nephronectin (Npnt) is an extracellular matrix protein and ligand of integrin α8β1 known to promote differentiation of osteoblasts. A search for factors that regulate Npnt gene expression in osteoblasts revealed that phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), had a strong effect to suppress that expression. Research was then conducted to elucidate the signaling pathway responsible for regulation of Npnt gene expression by PMA in osteoblasts. Treatment of MC3T3-E1 cells with PMA suppressed cell differentiation and Npnt gene expression. Effects were noted at a low concentration of PMA, and were time- and dose-dependent. Furthermore, treatment with the PKC signal inhibitor Gö6983 inhibited down-regulation of Npnt expression, while transfection with small interfering RNA (siRNA) of PKCα, c-Jun, and c-Fos suppressed that down-regulation. The present results suggest regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway.

Differential effects of protein kinase C on human vascular smooth muscle cell proliferation and migration

2001 ◽  
Vol 281 (1) ◽  
pp. H359-H370 ◽  
Author(s):  
Hiroyuki Itoh ◽  
Shinji Yamamura ◽  
J. Anthony Ware ◽  
Shaobin Zhuang ◽  
Shinsuke Mii ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Phorbol Ester ◽  
Inhibitory Effect ◽  
Kinase C ◽  
And Migration ◽  
Proliferation And Migration

Vascular smooth muscle cell (SMC) migration and proliferation contribute to intimal hyperplasia, and protein kinase C (PKC) may be required for both events. In this report, we investigated the role of PKC in proliferation and migration of SMC derived from the human saphenous vein. Activation of PKC by phorbol-12,13-dibutyrate (PDBu) or (−)-indolactam [(−)-ILV] increases SMC proliferation. Downregulation of PKC activity by prolonged incubation with phorbol ester or inhibition of PKC with chelerythrine in SMC diminished agonist-stimulated proliferation. In contrast, stimulation of PKC with PDBu or (−)-ILV inhibited basal and agonist-induced SMC chemotaxis. Moreover, downregulation of PKC or inhibition with chelerythrine accentuated migration. We postulated that the inhibitory effect of PKC on SMC chemotaxis was mediated through cAMP-dependent protein kinase (protein kinase A, PKA). In support of this hypothesis, we found that activation of PKC in SMC stimulated PKA activity. The cAMP agonist forskolin significantly inhibited SMC chemotaxis. Furthermore, the inhibitory effect of PKC on SMC chemotaxis was completely reversed by cAMP or PKA inhibitors. In search of the PKC isotype(s) underlying these differential effects of PKC in SMC, we identified eight isotypes expressed in human SMC. Only PKC-α, -βI, -δ, and -ε were eliminated by downregulation, suggesting that one or more of these four enzymes facilitate the observed phorbol ester-dependent effects of PKC in SMC. In summary, we found that PKC activation enhances proliferation but inhibits migration of human vascular SMC. These differential effect of PKC on vascular cells appears to be mediated through PKC-α, -βI, -δ, and/or -ε.

Endothelium stimulates the vascular smooth muscle cell Na/K pump of normotensive and hypertensive rats by a protein kinase C pathway

1996 ◽  
Vol 14 (11) ◽  
pp. 1301-1307 ◽  
Author(s):  
Juliana Redondo ◽  
M Angeles Rodr??guez-Mart??nez ◽  
Mar??a J. Alonso ◽  
Mercedes Salaices ◽  
Gloria Balfag??n ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Hypertensive Rats ◽  
Kinase C
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