scholarly journals Bidirectional regulation of renal cortical Na+,K+-ATPase by protein kinase C.

2004 ◽  
Vol 51 (3) ◽  
pp. 757-772 ◽  
Author(s):  
Jerzy Bełtowski ◽  
Andrzej Marciniak ◽  
Anna Jamroz-Wiśniewska ◽  
Ewelina Borkowska ◽  
Grazyna Wójcicka
Keyword(s):  
Cytochrome P450 ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Inhibitory Effect ◽  
Kinase C ◽  
Bidirectional Regulation ◽  
Male Wistar Rats ◽  
Arachidonate Metabolites ◽  
High Doses

We examined the role of protein kinase C (PKC) in the regulation of Na+,K+- ATPase activity in the renal cortex. Male Wistar rats were anaesthetized and the investigated reagents were infused into the abdominal aorta proximally to the renal arteries. A PKC-activating phorbol ester, phorbol 12,13-dibutyrate (PDBu), had a dose-dependent effect on cortical Na+,K+-ATPase activity. Low dose of PDBu (10(-11) mol/kg per min) increased cortical Na+,K+-ATPase activity by 34.2%, whereas high doses (10(-9) and 10(-8) mol/kg per min) reduced this activity by 22.7% and 35.0%, respectively. PDBu administration caused changes in Na+,K+-ATPase Vmax without affecting K(0.5) for Na+, K+ and ATP as well as Ki for ouabain. The effects of PDBu were abolished by PKC inhibitors, staurosporine, GF109203X, and Gö 6976. The inhibitory effect of PDBu was reversed by pretreatment with inhibitors of cytochrome P450-dependent arachidonate metabolism, ethoxyresorufin and 17-octadecynoic acid, inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and LY294002, and by actin depolymerizing agents, cytochalasin D and latrunculin B. These results suggest that PKC may either stimulate or inhibit renal cortical Na+,K+-ATPase. The inhibitory effect is mediated by cytochrome P450-dependent arachidonate metabolites and PI3K, and is caused by redistribution of the sodium pump from the plasma membrane to the inactive intracellular pool.

Na+-K+-ATPase is an effector protein for protein kinase C in renal proximal tubule cells

1989 ◽  
Vol 256 (2) ◽  
pp. F370-F373 ◽  
Author(s):  
A. Bertorello ◽  
A. Aperia
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Sodium Transport ◽  
Phorbol Esters ◽  
Inhibitory Effect ◽  
Proximal Tubule Cells ◽  
Kinase C ◽  
Dependent Inhibition ◽  
Renal Proximal Tubule Cells

Activators of protein kinase C (PKC) inhibit sodium transport in proximal tubules (PT) (M. Baum and S. R. Hays. Am. J. Physiol. 254 (Renal Fluid Electrolyte Physiol. 23): F9-F14, 1988. In this study we have evaluated the effect of PKC activators on the enzyme responsible for active sodium transport, Na+-K+-ATPase. Both endogenous (diacylglycerol, DAG) and exogenous (phorbol esters, PE) activators were used. Enzyme activity was determined in permeabilized single PT segments. In vehicle-incubated PT, Na+-K+-ATPase activity (pmol Pi.mm tubule-1.-1 h) was 1,403 +/- 128. The synthetic DAG, L-alpha-l-oleoyl-2-acetoyl-sn-3-glycerol (10(-4) M) significantly inhibited Na+-K+-ATPase activity to 673 +/- 51, P less than 0.05. The PE-phorbol 12,13-dibutyrate (PDBu), induced a time- and dose-dependent inhibition of Na+-K+-ATPase activity. Inhibition was significant at 15 and maximal at 20 min. Na+-K+-ATPase activity in PT incubated with PDBu was 796 +/- 171 (10(-8) M), 570 +/- 198 (10(-7) M), and 484 +/- 130 (10(-6) M). A PE that does not activate PKC, 4-alpha-phorbol didecanoate, did not inhibit Na+-K+-ATPase activity. PDBu 10(-7) M had no effect on purified Na+-K+-ATPase. Sphingosine (SP), a PKC inhibitor, abolished the inhibitory effect of PDBu (10(-7) M) on Na+-K+-ATPase activity. Dopamine (DA) is a physiological inhibitor of Na+-K+-ATPase activity in PT [A. Bertorello, T. Hokfelt, M. Goldstein, and A. Aperia Am. J. Physiol. 254(Renal Fluid Electrolyte Physiol. 23): F795-F801, 1988].(ABSTRACT TRUNCATED AT 250 WORDS)

Osmotic Modulation of the Ouabain-Sensitive (Na++K+)ATPase from Malpighian Tubules of Rhodnius prolixus

1998 ◽  
Vol 53 (9-10) ◽  
pp. 911-917 ◽  
Author(s):  
C. Caruso-Neves ◽  
J. R. Meyer-Fernandes ◽  
A. G. Lopes
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Malpighian Tubule ◽  
Inhibitory Effect ◽  
Rhodnius Prolixus ◽  
Malpighian Tubules ◽  
Maximal Effect ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

The presence and regulation by hyperosmotic medium of the ouabain-sensitive (Na++K+)ATPase of the Malpighian tubule cells of Rhodnius prolixus was investigated. The ouabain-sensitive (Na++K+)ATPase activity was 5.4 ± 0.5 nmol Pi x mg-1 x min-1. Vanadate 100 μM completely abolished this ATPase activity. In hyperosmotic medium, obtained by addition of 180 mᴍ mannitol, the (Na++K+)ATPase activity was inhibited by 60%. When the cell lysates were preincubated in hyperosmotic medium for 30 minutes and the ATPase activity was assayed in isosmotic medium, the (Na++K+)ATPase activity was not modified. Addition of 50 ng/ml sphingosine, a protein kinase C inhibitor, abolished the inhibition of (Na++K+)ATPase activity in hyperosmotic medium. Furtherm ore, phorbol ester (TPA), an activator of protein kinase C, mimicked the effect of hyperosmotic shock on (Na++K+)ATPase activity. The increase in Ca2+ concentration decreased the (Na++K+)ATPase activity by 60% in isosmotic medium, with maximal effect obtained in 10-6 m Ca2+. No effect was observed in hyperosmotic medium. The inhibitory effect of Ca2+ on the (Na++K+)ATPase was not reversed by sphingosine. These results indicate that the ouabain-sensitive (Na++K+) ATPase activity of the Malpighian tubule is regulated by both increasing Ca2+ concentration and by the osmolality of the medium by different and integrative ways.

Inhibitory Effect of Barbiturates and Local Anaesthetics on Protein Kinase C Activation

1990 ◽  
Vol 18 (2) ◽  
pp. 153-160 ◽  
Author(s):  
K. Mikawa ◽  
N. Maekawa ◽  
H. Hoshina ◽  
O. Tanaka ◽  
J. Shirakawa ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Local Anaesthetics ◽  
Inhibitory Effect ◽  
Kinase C ◽  
Protein Kinase C Activation

scholarly journals Protein kinase C-α inhibits the repair of oxidative phosphorylation after S-(1,2-dichlorovinyl)-l-cysteine injury in renal cells

2004 ◽  
Vol 287 (1) ◽  
pp. F64-F73 ◽  
Author(s):  
Xiuli Liu ◽  
Malinda L. Godwin ◽  
Grażyna Nowak
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Mitochondrial Function ◽  
Recovery Period ◽  
Β Subunit ◽  
Atp Production ◽  
Kinase C ◽  
Mitochondrial Functions

Previously, we showed that physiological functions of renal proximal tubular cells (RPTC) do not recover following S-(1,2-dichlorovinyl)-l-cysteine (DCVC)-induced injury. This study investigated the role of protein kinase C-α (PKC-α) in the lack of repair of mitochondrial function in DCVC-injured RPTC. After DCVC exposure, basal oxygen consumption (Qo2), uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production decreased, respectively, to 59, 27, 27, 57, and 68% of controls. None of these functions recovered. Mitochondrial transmembrane potential decreased 53% after DCVC injury but recovered on day 4. PKC-α was activated 4.3- and 2.5-fold on days 2 and 4, respectively, of the recovery period. Inhibition of PKC-α activation (10 nM Go6976) did not block DCVC-induced decreases in mitochondrial functions but promoted the recovery of uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production. Protein levels of the catalytic β-subunit of F1F0-ATPase were not changed by DCVC or during the recovery period. Amino acid sequence analysis revealed that α-, β-, and ε-subunits of F1F0-ATPase have PKC consensus motifs. Recombinant PKC-α phosphorylated the β-subunit and decreased F1F0-ATPase activity in vitro. Serine but not threonine phosphorylation of the β-subunit was increased during late recovery following DCVC injury, and inhibition of PKC-α activation decreased this phosphorylation. We conclude that during RPTC recovery following DCVC injury, 1) PKC-α activation decreases F0F1-ATPase activity, oxidative phosphorylation, and ATP production; 2) PKC-α phosphorylates the β-subunit of F1F0-ATPase on serine residue; and 3) PKC-α does not mediate depolarization of RPTC mitochondria. This is the first report showing that PKC-α phosphorylates the catalytic subunit of F1F0-ATPase and that PKC-α plays an important role in regulating repair of mitochondrial function.

Inhibitory Effect of Hypocrellin A on Protein Kinase C in Liver and Skeletal Muscle of Obese Zucker Rats

2003 ◽  
Vol 31 (06) ◽  
pp. 871-878 ◽  
Author(s):  
Xianqin Qu ◽  
Lei Dang ◽  
J. Paul Seale
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Inhibitory Effect ◽  
Zucker Rats ◽  
Dependent Manner ◽  
Kinase C ◽  
Hypocrellin A ◽  
Pkc Isoforms ◽  
Obese Zucker Rats

In this ex vivo study, the inhibitory activity of hypocrellin A (HA), a perylene quinonoid pigment isolated from the Chinese medicinal fungus Hypocrella bambuase, on protein kinase C (PKC) enzyme activity in insulin target tissues of obese Zucker rats was assessed. Pre-incubation with HA for 30 minutes significantly inhibited the activity of partially purified PKC enzyme from liver and soleus skeletal muscle in a dose-dependent manner ( IC 50=0.07 and 0.26 μg/ml, respectively). HA produced a greater inhibitory effect in enzyme prepared from the liver than enzyme prepared from soleus muscle. Since total PKC activity in these two insulin target tissues is the net result of several different isoforms of PKC, and PKC-θ is a major isoform expressed in the soleus skeletal muscle, the present data suggest that the naturally occurring compound, HA, may selectively inhibit certain PKC isoforms other than PKC-θ. Further investigations are required to determine which PKC isoforms are most susceptible to HA and whether changes in PKC signaling during treatment with HA can reverse abnormalities of glucose and lipid metabolism in insulin resistant and diabetic states.

scholarly journals Protein kinase C in rod outer segments: effects of phosphorylation of the phosphodiesterase inhibitory subunit

1996 ◽  
Vol 317 (1) ◽  
pp. 291-295 ◽  
Author(s):  
Igor P. UDOVICHENKO ◽  
Jess CUNNICK ◽  
Karen GONZALEZ ◽  
Alexander YAKHNIN ◽  
Dolores J. TAKEMOTO
Keyword(s):  
Protein Kinase C ◽  
Catalytic Activity ◽  
Protein Kinase ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Rod Outer Segments ◽  
Visual Transduction ◽  
Gtp Hydrolysis ◽  
Outer Segments ◽  
Kinase C

The inhibitory subunit (PDEγ) of the cGMP phosphodiesterase (PDEαβγ2) in rod outer segments (ROS) realizes its regulatory role in phototransduction by inhibition of PDEαβ catalytic activity. The photoreceptor G-protein, transducin, serves as a transducer from the receptor (rhodopsin) to the effector (PDE) and eliminates the inhibitory effect of PDEγ by direct interaction with PDEγ. Our previous study [Udovichenko, Cunnick, Gonzalez and Takemoto (1994) J. Biol. Chem. 269, 9850–9856] has shown that PDEγ is a substrate for protein kinase C (PKC) from ROS and that phosphorylation by PKC increases the ability of PDEγ to inhibit PDEαβ catalytic activity. Here we report that transducin is less effective in activation of PDEαβ(γp)2 (a complex of PDEαβ with phosphorylated PDEγ, PDEγp) than PDEαβγ2. PDEγp also increases the rate constant of GTP hydrolysis of transducin (from 0.16 s-1 for non-phosphorylated PDEγ to 0.21 s-1 for PDEγp). These data suggest that phosphorylation of the inhibitory subunit of PDE by PKC may regulate the visual transduction cascade by decreasing the photoresponse.

Two Interacting Signal Transduction Pathways Regulate Collecting Duct Water Transport

Physiology ◽  
1988 ◽  
Vol 3 (6) ◽  
pp. 235-241 ◽  
Author(s):  
Y Ando ◽  
HR Jacobson ◽  
MD Breyer
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Cell Function ◽  
Collecting Duct ◽  
Signal Transduction Pathways ◽  
Phosphatidylinositol Bisphosphate ◽  
Kinase C ◽  
Arachidonate Metabolites

Receptor-mediated signal transduction occurs through phosphatidylinositol bisphosphate (PIP2) breakdown and activation of adenylate cyclase interacting to regulate cell function. Current studies suggest that hormone-stimulated PIP2 breakdown modulates the classic cyclic AMP-mediated hydrosmotic action of vasopressin through separate mechanisms attributable to activation of protein kinase C, elevation of intracellular Ca2+ concentration, and generation of arachidonate metabolites.

Autoregulation of muscarinic and gastrin receptors on gastric parietal cells

1989 ◽  
Vol 256 (2) ◽  
pp. G356-G363 ◽  
Author(s):  
T. Chiba ◽  
S. K. Fisher ◽  
B. W. Agranoff ◽  
T. Yamada
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Parietal Cell ◽  
Phorbol Esters ◽  
Cell Function ◽  
Inhibitory Effect ◽  
Parietal Cells ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Inositol Phospholipids

In previous studies we demonstrated that parietal cell stimulation with gastrin and carbamoylcholine (carbachol) is accompanied by increased turnover of membrane inositol phospholipids. We conducted the present studies to examine whether membrane-associated protein kinase C activity is enhanced as a consequence of these events and to explore the role of this enzyme in regulating parietal cell function. We observed that carbachol and gastrin dose dependently increased membrane-associated protein kinase C activity while histamine did not. Furthermore, compounds such as phorbol esters and diacylglycerol, which are known to be direct stimulants of protein kinase C activity, also stimulated parietal cell aminopyrine uptake. In contrast, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the synthetic diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol inhibited both aminopyrine uptake and membrane inositol phospholipid turnover in parietal cells induced by carbachol and gastrin. The inhibitory effect appeared to result from reduction in the quantity of muscarinic and gastrin receptors without alterations in their specific affinities. These data suggest that protein kinase C mediates stimulation of parietal cells by gastrin and carbachol but also activates an autoregulatory mechanism via downregulation of muscarinic and gastrin receptors.

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