scholarly journals Excitatory Roles of Protein Kinase C in Striatal Cholinergic Interneurons

2009 ◽  
Vol 102 (4) ◽  
pp. 2453-2461 ◽  
Author(s):  
Ping Deng ◽  
Zhi-Ping Pang ◽  
Zhigang Lei ◽  
Zao C. Xu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Metabotropic Glutamate Receptors ◽  
Neuronal Excitability ◽  
Delayed Rectifier ◽  
Striatal Neurons ◽  
Cholinergic Interneurons ◽  
Kinase C ◽  
Group I ◽  
Pkc Activation

Protein kinase C (PKC) plays critical roles in neuronal activity and is widely expressed in striatal neurons. However, it is not clear how PKC activation regulates the excitability of striatal cholinergic interneurons. In the present study, we found that PKC activation significantly inhibited A-type potassium current ( IA), but had no effect on delayed rectifier potassium currents. Consistently, application of PKC activator caused an increase of firing in response to depolarizing currents in cholinergic interneurons, which was persistent in the presence of both excitatory and inhibitory neurotransmission blockers. These excitatory effects of PKC could be partially mimicked and occluded by blockade of IA with potassium channel blocker 4-aminopyridine. In addition, immunostaining demonstrated that PKCα, but not PKCγ and PKCε, was expressed in cholinergic interneurons. Furthermore, activation of group I metabotropic glutamate receptors (mGluRs) led to an inhibition of IA through a PKC-dependent pathway. These data indicate that activation of PKC, most likely PKCα, increases the neuronal excitability of striatal cholinergic interneurons by down-regulating IA. Group I mGluR-mediated IA inhibition might be important for the glutamatergic regulation of cholinergic tone in the neostriatum.

scholarly journals Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation

1999 ◽  
Vol 277 (3) ◽  
pp. L558-L565 ◽  
Author(s):  
Scott A. Barman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Channel Blocker ◽  
Pressor Response ◽  
Vascular Occlusion ◽  
Membrane Depolarization ◽  
Delayed Rectifier ◽  
Vascular Compliance ◽  
Kinase C ◽  
Pkc Activation

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10−7 M) and thymeleatoxin (THX; 10−7 M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10−5 M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10−4 M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10−5 M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

Modulation of Transient and Persistent Inward Currents by Activation of Protein Kinase C in Spinal Ventral Neurons of the Neonatal Rat

2009 ◽  
Vol 101 (1) ◽  
pp. 112-128 ◽  
Author(s):  
Yue Dai ◽  
Larry M. Jordan ◽  
Brent Fedirchuk
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuronal Excitability ◽  
Cell Voltage ◽  
Decay Rates ◽  
Half Width ◽  
Neonatal Rat ◽  
Kinase C ◽  
Maximal Rise ◽  
Pkc Activation

Neuronal excitability can be regulated through modulation of voltage threshold ( Vth). Previous studies suggested that this modulation could be mediated by modulation of transient sodium currents ( IT) and/or persistent inward current (PIC). Modulation of IT and PIC through activation of protein kinase C (PKC) has previously been described as a mechanism controlling neuronal excitability. We investigated modulation of IT and PIC by PKC in neonatal rat spinal ventral neurons. In whole cell voltage clamp, activation of PKC by application of 1-oleoyl-2-acetyl-sn-glycerol (OAG, 10–30 μM) resulted in 1) a reduction of IT amplitude by 33% accompanied an increase in half-width and a decrease in the maximal rise and decay rates of the IT; 2) a reduction of PIC amplitude by 49%, with a depolarization of PIC onset by 4.5 mV. Activation of PKC caused varied effects on Vth for eliciting IT, with an unchanged Vth or depolarized Vth being the most common effects. In current-clamp recordings, PKC activation produced a small but significant depolarization (2.0 mV) of Vth for action potential generation with an increase in half-width and a decrease in amplitude and the maximal rise and decay rates of action potentials. Inclusion of PKCI19–36 (10–30 μM), a PKC inhibitor, in the recording pipette could block the OAG effects on IT and PIC. The ability of serotonin to hyperpolarize Vth was not altered by PKC activation or inhibition. This study demonstrates that activation of PKC decreases the excitability of spinal ventral neurons and that Vth can be modulated by multiple mechanisms.

Contrasting Roles of Protein Kinase C in Induction Versus Suppression of Group I mGluR-Mediated Epileptogenesis In Vitro

2005 ◽  
Vol 94 (5) ◽  
pp. 3643-3647 ◽  
Author(s):  
John C. Cuellar ◽  
Elvin L. Griffith ◽  
Lisa R. Merlin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Burst Length ◽  
Metabotropic Glutamate ◽  
Kinase C ◽  
Group I ◽  
Group I Mglurs

Activation of group I metabotropic glutamate receptors (mGluRs) elicits persistent ictaform discharges in guinea pig hippocampal slices, providing an in vitro model of epileptogenesis. The induction of these persistent ictaform bursts is prevented by l-cysteine sulfinic acid (CSA), an agonist at phospholipase D (PLD)–coupled mGluRs. Studies described herein examined the role of protein kinase C (PKC) in both the group I mGluR–mediated induction and CSA-mediated suppression of this form of epileptogenesis. Intracellular recordings were performed from CA3 stratum pyramidale and synchronized burst length was monitored. In the presence of 50 μM picrotoxin, a γ-aminobutyric acid type A antagonist, 250- to 500-ms synchronized bursts were elicited. ( S)-3,5-Dihydroxyphenylglycine (DHPG, 50 μM), an agonist at group I mGluRs, increased the burst length to 1–3 s in duration, a change that persisted after agonist washout. This persistent change in burst length was elicited in the presence of 10 μM chelerythrine, a PKC inhibitor, indicating that DHPG-induced epileptogenesis is PKC independent. However, although PLD activation with CSA (100 μM) was highly effective at suppressing group I mGluR–mediated induction of burst prolongation, CSA application in the presence of chelerythrine was no longer effective and resulted in the expression of persistent ictaform bursts. These data suggest that CSA-mediated suppression of group I mGluR–induced epileptogenesis is PKC dependent. We propose that CSA mediates its effect by PLD-driven activation of PKC, which may desensitize the phospholipase C–linked group I mGluRs and thereby prevent group I mGluR–induced epileptogenesis.

Endotoxin-Induced Tissue Factor in Human Monocytes is Dependent upon Protein Kinase C Activation

1993 ◽  
Vol 70 (05) ◽  
pp. 800-806 ◽  
Author(s):  
C Ternisien ◽  
M Ramani ◽  
V Ollivier ◽  
F Khechai ◽  
T Vu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tissue Factor ◽  
Factor Ix ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Kinase C ◽  
Pkc Activation

SummaryTissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

Phosphorylation by protein kinase C stabilizes ABCG1 and increases cholesterol efflux

2019 ◽  
Vol 166 (4) ◽  
pp. 309-315 ◽  
Author(s):  
Taro Watanabe ◽  
Noriyuki Kioka ◽  
Kazumitsu Ueda ◽  
Michinori Matsuo
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Translational Regulation ◽  
Cholesterol Efflux ◽  
Degradation Rate ◽  
Active Form ◽  
Density Lipoprotein ◽  
Protein Levels ◽  
Kinase C ◽  
Pkc Activation

Abstract ATP-binding cassette protein G1 (ABCG1) plays an important role in eliminating excess cholesterol from macrophages and in the formation of high-density lipoprotein (HDL), which contributes to the prevention and regression of atherosclerosis. The post-translational regulation of ABCG1 remains elusive, although phosphorylation by protein kinase A destabilizes ABCG1 proteins. We examined the phosphorylation of ABCG1 using HEK293 and Raw264.7 cells. ABCG1 phosphorylation was enhanced by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator. PKC activation by TPA increased ABCG1 protein levels and promoted ABCG1-dependent cholesterol efflux to HDL. This activity was suppressed by Go6976, a PKCα/βI inhibitor, suggesting that PKC activation stabilizes ABCG1. To confirm this, the degradation rate of ABCG1 was analysed; ABCG1 degradation was suppressed upon PKC activation, suggesting that PKC phosphorylation regulates ABCG1 levels. To confirm this involvement, we co-expressed ABCG1 and a constitutively active form of PKCα in HEK cells. ABCG1 was increased upon co-expression. These results suggest that PKC-mediated phosphorylation, probably PKCα, stabilizes ABCG1, consequently increasing ABCG1-mediated cholesterol efflux, by suppressing ABCG1 degradation. PKC activation could thus be a therapeutic target to suppress the development of atherosclerosis.

scholarly journals Requirement for diacylglycerol and protein kinase C in HeLa cell-substratum adhesion and their feedback amplification of arachidonic acid production for optimum cell spreading.

1993 ◽  
Vol 4 (3) ◽  
pp. 271-281 ◽  
Author(s):  
J S Chun ◽  
B S Jacobson
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Hela Cell ◽  
Cell Attachment ◽  
Cell Spreading ◽  
Subsequent Formation ◽  
Sequence Of Events ◽  
Kinase C ◽  
Pkc Activation

Release of arachidonic acid (AA) and subsequent formation of a lipoxygenase (LOX) metabolite(s) is an obligatory signal to induce spreading of HeLa cells on a gelatin substratum (Chun and Jacobson, 1992). This study characterizes signaling pathways that follow the LOX metabolite(s) formation. Levels of diacylglycerol (DG) increase upon attachment and before cell spreading on a gelatin substratum. DG production and cell spreading are insignificant when phospholipase A2 (PLA2) or LOX is blocked. In contrast, when cells in suspension where PLA2 activity is not stimulated are treated with exogenous AA, DG production is turned on, and inhibition of LOX turns it off. This indicates that the formation of a LOX metabolite(s) from AA released during cell attachment induces the production of DG. Consistent with the DG production is the activation of protein kinase C (PKC) which, as with AA and DG, occurs upon attachment and before cell spreading. Inhibition of AA release and subsequent DG production blocks both PKC activation and cell spreading. Cell spreading is also blocked by the inhibition of PKC with calphostin C or sphingosine. The inhibition of cell spreading induced by blocking AA release is reversed by the direct activation of PKC with phorbol ester. However, the inhibition of cell spreading induced by PKC inhibition is not reversed by exogenously applied AA. In addition, inhibition of PKC does not block AA release and DG production. The data indicate that there is a sequence of events triggered by HeLa cell attachment to a gelatin substratum that leads to the initiation of cell spreading: AA release, a LOX metabolite(s) formation, DG production, and PKC activation. The data also provide evidence indicating that HeLa cell spreading is a cyclic feedback amplification process centered on the production of AA, which is the first messenger produced in the sequence of messengers initiating cell spreading. Both DG and PKC activity that are increased during HeLa cell attachment to a gelatin substratum appear to be involved. DG not only activates PKC, which is essential for cell spreading, but is also hydrolyzed to AA. PKC, which is initially activated as consequence of AA production, also increases more AA production by activating PLA2.

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