Short-term regulation of renal Na-K-ATPase activity: physiological relevance and cellular mechanisms

1993 ◽  
Vol 265 (6) ◽  
pp. F743-F755 ◽  
Author(s):  
A. M. Bertorello ◽  
A. I. Katz
Keyword(s):  
Protein Kinase ◽  
Atpase Activity ◽  
Renal Tubules ◽  
Short Term ◽  
Cellular Mechanisms ◽  
Sodium Potassium ◽  
Kinase C ◽  
Physiological Relevance ◽  
Intracellular Messengers ◽  
Intracellular Signal

Sodium-potassium-activated adenosinetriphosphatase (Na-K-ATPase; the Na:K pump), located at the basolateral domain of epithelial cells, provides the driving force for active sodium and potassium translocation and for the secondary active transport of other solutes across the renal tubules. Short-term regulation of renal Na-K-ATPase activity (i.e., not reflecting changes in its biosynthesis rate) provides an important mechanism of modulating tubule transport and thus the final Na and K urinary excretion. Recent studies have provided abundant evidence that such regulation is effected by complex functional networks that are specific for different nephron segments and involve distinct and often mutually interacting intracellular signal transduction pathways. The effects of hormones and autacoids linked to alterations in cell adenosine 3',5'-cyclic monophosphate and consequently of protein kinase A, in the levels and distribution of protein kinase C, or in the generation of various eicosanoids provide examples of rapid Na:K pump activity modulation by the mechanisms mentioned above. In this review we assess the roles of specific intracellular messengers and the manner in which they, and especially protein kinases, might interact with the pump in the short-term regulation of its activity; also, we examine the emerging evidence supporting the participation of the cytoskeleton in this process.

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.

Down-regulation of protein kinase C and kinase inhibitors dissociate short- and long-term enhancement produced by one-trial conditioning of Hermissenda

1993 ◽  
Vol 69 (2) ◽  
pp. 636-641 ◽  
Author(s):  
T. Crow ◽  
J. Forrester
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cellular Plasticity ◽  
Short Term ◽  
Down Regulation ◽  
Kinase C ◽  
Short And Long Term

1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.

scholarly journals The substrates and binding partners of protein kinase Cε

2010 ◽  
Vol 427 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Philip M. Newton ◽  
Robert O. Messing
Keyword(s):  
Protein Kinase ◽  
Active Drug ◽  
Major Research ◽  
Research Focus ◽  
Cellular Mechanisms ◽  
Future Studies ◽  
Kinase C ◽  
Binding Partners ◽  
Signalling Cascades ◽  
Substrate Phosphorylation

The ε isoform of protein kinase C (PKCε) has important roles in the function of the cardiac, immune and nervous systems. As a result of its diverse actions, PKCε is the target of active drug-discovery programmes. A major research focus is to identify signalling cascades that include PKCε and the substrates that PKCε regulates. In the present review, we identify and discuss those proteins that have been conclusively shown to be direct substrates of PKCε by the best currently available means. We will also describe binding partners that anchor PKCε near its substrates. We review the consequences of substrate phosphorylation and discuss cellular mechanisms by which target specificity is achieved. We begin with a brief overview of the biology of PKCε and methods for substrate identification, and proceed with a discussion of substrate categories to identify common themes that emerge and how these may be used to guide future studies.

Regulation of Na+-K+ Pump Activity: Pathways Between Receptors and Effectors

Physiology ◽  
1995 ◽  
Vol 10 (6) ◽  
pp. 253-259 ◽  
Author(s):  
AM Bertorello ◽  
AI Katz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Short Term ◽  
Dependent Protein Kinase ◽  
Regulatory Pathways ◽  
Kinase C ◽  
Intracellular Signals ◽  
Pump Activity ◽  
Dependent Protein ◽  
A Subunit

Short-term regulation of membrane Na+ -K+-ATPase activity is achieved by complex networks of receptor-mediated intracellular signals. Such regulatory pathways include activation of cyclic AMP-dependent protein kinase or protein kinase C and involve reversible phosphorylation of the catalytic (a) subunit of the enzyme directly, of additional mediators like eicosanoids and the actin cytoskeleton, or both.

Endothelin stimulates Na(+)-K(+)-ATPase activity by a protein kinase C-dependent pathway in rabbit aorta

1991 ◽  
Vol 261 (1) ◽  
pp. H38-H45 ◽  
Author(s):  
S. Gupta ◽  
N. B. Ruderman ◽  
E. J. Cragoe ◽  
I. Sussman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Rabbit Aorta ◽  
Effective Concentration ◽  
Kinase C ◽  
Exchange Inhibitor ◽  
Half Maximal Effective Concentration ◽  
Dependent Pathway ◽  
Stimulation Of

Incubation with endothelin (Endo) caused a time- and concentration-dependent increase in both ouabain-sensitive (OS) and ouabain-insensitive (OI) 86Rb+ uptake [half-maximal effective concentration (EC50) for OS component = 11 nM] in the rabbit aorta. Increase in the OS component [Na(+)-K(+)-adenosine triphosphatase (ATPase) activity] accounted for 70% of the 110% increase in total 86Rb+ uptake at a maximally effective concentration of Endo (100 nM). Protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBU; 100 nM) increased total 86Rb+ uptake by 69%, with 42% of the increase in the OS component. Stimulation by Endo and PDBU was not additive. Staurosporine (STA; 100 nM) inhibited stimulation of total 86Rb+ uptake by Endo and PDBU by approximately 60%. With ouabain and STA added together, inhibition of Endo-stimulated total 86Rb+ uptake (90%) was greater than with either agent alone, suggesting that STA inhibits an OS as well as an OI component of 86Rb+ uptake. Stimulation of total 86Rb+ uptake by both Endo and PDBU were also inhibited by approximately 60% by the Na(+)-H+ exchange inhibitor 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Endo-stimulated total 86Rb+ uptake was not further inhibited when ouabain was added together with EIPA, suggesting that Na(+)-H+ exchange is primarily linked to the OS component of 86Rb+ uptake. In contrast, Na(+)-K(+)-Cl- cotransport inhibitor bumetanide inhibited increases in total 86Rb+ uptake caused by Endo (30%) and PDBU (56%) due solely to its effects on OI 86Rb+ uptake. Results suggest that Endo stimulates Na(+)-K(+)-ATPase activity in rabbit aorta by activating PKC and Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Aldosterone stimulates vacuolar H+-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway

2011 ◽  
Vol 301 (5) ◽  
pp. C1251-C1261 ◽  
Author(s):  
Christian Winter ◽  
Nicole B. Kampik ◽  
Luca Vedovelli ◽  
Florina Rothenberger ◽  
Teodor G. Păunescu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Intracellular Signaling ◽  
Collecting Duct ◽  
Intercalated Cells ◽  
Nongenomic Action ◽  
Kinase C ◽  
Urinary Acidification ◽  
Stimulation Of

Urinary acidification in the collecting duct is mediated by the activity of H+-ATPases and is stimulated by various factors including angiotensin II and aldosterone. Classically, aldosterone effects are mediated via the mineralocorticoid receptor. Recently, we demonstrated a nongenomic stimulatory effect of aldosterone on H+-ATPase activity in acid-secretory intercalated cells of isolated mouse outer medullary collecting ducts (OMCD). Here we investigated the intracellular signaling cascade mediating this stimulatory effect. Aldosterone stimulated H+-ATPase activity in isolated mouse and human OMCDs. This effect was blocked by suramin, a general G protein inhibitor, and GP-2A, a specific Gαq inhibitor, whereas pertussis toxin was without effect. Inhibition of phospholipase C with U-73122, chelation of intracellular Ca2+ with BAPTA, and blockade of protein kinase C prevented the stimulation of H+-ATPases. Stimulation of PKC by DOG mimicked the effect of aldosterone on H+-ATPase activity. Similarly, aldosterone and DOG induced a rapid translocation of H+-ATPases to the luminal side of OMCD cells in vivo. In addition, PD098059, an inhibitor of ERK1/2 activation, blocked the aldosterone and DOG effects. Inhibition of PKA with H89 or KT2750 prevented and incubation with 8-bromoadenosine-cAMP mildly increased H+-ATPase activity. Thus, the nongenomic modulation of H+-ATPase activity in OMCD-intercalated cells by aldosterone involves several intracellular pathways and may be mediated by a Gαq protein-coupled receptor and PKC. PKA and cAMP appear to have a modulatory effect. The rapid nongenomic action of aldosterone may participate in the regulation of H+-ATPase activity and contribute to final urinary acidification.

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