Sex Differences in Rat Hepatic Cytolethality of the Protein Kinase C Inhibitor Safingol: Role of Biotransformation

1996 ◽  
Vol 137 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Mark A. Carfagna ◽  
Karen M. Young ◽  
Robert L. Susick, Jr.
Keyword(s):  
Sex Differences ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

scholarly journals Continuous Activation of Gαq in Osteoblasts Results in Osteopenia through Impaired Osteoblast Differentiation

2007 ◽  
Vol 282 (49) ◽  
pp. 35757-35764 ◽  
Author(s):  
Naoshi Ogata ◽  
Hiroshi Kawaguchi ◽  
Ung-il Chung ◽  
Sanford I. Roth ◽  
Gino V. Segre
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Trabecular Thickness ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Skeletal Homeostasis ◽  
Trabecular Bones ◽  
Constitutively Active

We explored the role of Gαq-mediated signaling on skeletal homeostasis by selectively expressing a constitutively active Gαq (mutation of Q209L) in osteoblasts. Continuous signaling via Gαq in mouse osteoblastic MC3T3-E1 cells impaired differentiation. Mice that expressed the constitutively active Gαq transgene in cells of the osteoblast lineage exhibited severe osteopenia in cortical and trabecular bones. Osteoblast number, bone volume, and trabecular thickness were reduced in transgenic mice, but the osteoclasts were unaffected. Osteoblasts from transgenic mice showed impaired differentiation and matrix formation. In the presence of a protein kinase C inhibitor GF109203X, this impairment was not seen, indicating mediation by the protein kinase C pathway. We propose that continuous activation of the Gαq signal in osteoblasts plays a crucial, previously unrecognized role in bone formation.

Localization of IP in rabbit kidney and functional role of the PGI2/IP system in cortical collecting duct

2002 ◽  
Vol 283 (4) ◽  
pp. F689-F698 ◽  
Author(s):  
Rania Nasrallah ◽  
Rolf M. Nusing ◽  
Richard L. Hébert
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Functional Role ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Rabbit Kidney ◽  
Cortical Collecting Duct ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

To clarify the role of the PGI2/PGI2 receptor (IP) system in rabbit cortical collecting duct (RCCD), we characterized the expression of IP receptors in the rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein was detectable in all three regions of the kidney. To determine how PGI2 signals, we compared the effects of different PGI2 analogs [iloprost (ILP), carba-prostacyclin (c-PGI2), and cicaprost (CCP)] in the isolated perfused RCCD. PGI2 analogs did not increase water flow ( L p). Although PGI2 analogs did not reduce an established L p response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated L p by 45%. The inhibitory effect of ILP and c-PGI2 on AVP-stimulated L p is partially reversed by the protein kinase C inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca2+concentration ([Ca2+]i), but, in the presence of CCP, individual infusion of ILP and PGE2 increased [Ca2+]i, suggesting that CCP did not cause desensitization to either ILP or PGE2. We concluded that ILP and c-PGI2 activate PKC and the liberation of [Ca2+]i but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI2 effects but not CCP in RCCD.

scholarly journals Exogenous sphingosine 1-phosphate and sphingosylphosphorylcholine do not stimulate phospholipase D in C6 glioma cells.

1999 ◽  
Vol 46 (1) ◽  
pp. 99-106 ◽  
Author(s):  
A Dygas ◽  
M Sidorko ◽  
M Bobeszko ◽  
J Barańska
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase D ◽  
C6 Glioma Cells ◽  
C6 Cells ◽  
Glioma C6 ◽  
Kinase C ◽  
Sphingosine 1 Phosphate ◽  
Protein Kinase C Inhibitor

In the present study we investigate the effect of exogenous sphingosine, sphingosine 1-phosphate and sphingosylphosphorylcholine on phospholipase D (PLD) activity in glioma C6 cells. The cells were prelabeled with [1-14C]palmitic acid and PLD-mediated synthesis of [14C]phosphatidylethanol was measured. Sphingosine 1-phosphate and sphingosylphosphorylcholine did not stimulate [14C]phosphatidylethanol formation either at low (0.1-10 microM) or high (25-100 microM) concentrations. On the other hand, sphingosine at concentrations of 100-250 microM strongly stimulated PLD activity as compared to the effect of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), known as a PLD activator. The effect of TPA on PLD is linked to the activation of protein kinase C. The present study also shows that sphingosine additively enhances TPA-mediated PLD activity. This is in contrast to the postulated role of sphingosine as a protein kinase C inhibitor. These results demonstrate that in glioma C6 cells sphingosine not only affects PLD independently of its effect on protein kinase C, but also is unable to block TPA-mediated PLD activity.

Protein kinase C is not involved in alpha 1-adrenoceptor-mediated positive inotropic effect

1991 ◽  
Vol 260 (1) ◽  
pp. H27-H36 ◽  
Author(s):  
M. Endou ◽  
Y. Hattori ◽  
N. Tohse ◽  
M. Kanno
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Prolongation Of Action Potential ◽  
Electrophysiological Effects

This study was performed to determine whether activation of protein kinase C is responsible for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat papillary muscle. In the presence of 1 microM propranolol, phenylephrine (10 microM) produced triphasic inotropic response that was accompanied by prolongation of action potential duration (APD) and hyperpolarization of membrane potential. Phorbol 12,13-dibutyrate (PDBu, 0.1 microM) abolished the negative inotropic effect of phenylephrine and apparently resulted in enhancement of the positive inotropic effect. PDBu also attenuated the phenylephrine-induced hyperpolarization without affecting the APD prolongation. However, such changes were not observed with 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM). Neither PDBu nor TPA increased the force of contraction or prolonged APD similar to phenylephrine. The protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H 7, 10 microM) did not suppress the changes induced by PDBu, and more importantly H 7 did not affect the inotropic and electrophysiological effects of phenylephrine. Both TPA and PDBu significantly inhibited the phenylephrine-induced phosphoinositide hydrolysis as measured by [3H]inositol monophosphate, and these inhibitory effects were eliminated in the presence of H 7. Our results provide an argument against a role of protein kinase C activation in the alpha 1-adrenoceptor-mediated inotropic and electrophysiological effects.

Acute effects of glucose on reactivity of cerebral microcirculation: role of activation of protein kinase C

1995 ◽  
Vol 269 (4) ◽  
pp. H1297-H1302 ◽  
Author(s):  
W. G. Mayhan ◽  
K. P. Patel
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Acute Effects ◽  
Acute Hyperglycemia ◽  
Calphostin C ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Pial Arterioles ◽  
Cerebral Arterioles

Our first goal was to determine whether acute hyperglycemia alters endothelium-dependent reactivity of rat cerebral arterioles. Our second goal was to investigate a possible mechanism for impaired reactivity during acute hyperglycemia. Diameter of pial arterioles was measured during suffusion with ADP, acetylcholine, histamine, N-methyl-D-aspartate (NMDA), and nitroglycerin before and during application of a suffusate containing D-glucose (5, 10, 20, and 25 mM). ADP, acetylcholine, histamine, NMDA, and nitroglycerin produced dose-related vasodilation before application of D-glucose. Vasodilatation in response to the agonists was not altered by 5 and 10 mM D-glucose. In contrast, vasodilatation in response to ADP, acetylcholine, histamine, and NMDA was impaired during application of 20 and 25 mM D-glucose. Dilatation in response to nitroglycerin was not altered. Application of the protein kinase C inhibitor calphostin C (1.0 nM) or chelerythrine (10 nM) restored endothelium-dependent vasodilatation during application of 25 mM D-glucose. Thus acute hyperglycemia impairs endothelium-dependent responses of cerebral arterioles via the activation of protein kinase C.

scholarly journals Inhibition of Neutrophil Apoptosis by Verotoxin 2 Derived from Escherichia coli O157:H7

1999 ◽  
Vol 67 (11) ◽  
pp. 6203-6205 ◽  
Author(s):  
Jiajia Liu ◽  
Tohru Akahoshi ◽  
Takeshi Sasahana ◽  
Hidero Kitasato ◽  
Rie Namai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Neutrophil Apoptosis ◽  
Escherichia Coli O157 ◽  
Significant Delay ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

ABSTRACT In order to evaluate the pathological role of verotoxin 2 (VT2), we investigated the effects of VT2 on neutrophil apoptosis in vitro. The results showed that VT2 caused a significant delay in spontaneous neutrophil apoptosis and that the effect was abrogated by a protein kinase C inhibitor. These data indicate that longer survival of neutrophils may aggravate neutrophil-mediated tissue damage in VT2-associated diseases.

Role of protein kinase C in the regulation of steroidogenesis in the mouse Leydig cell

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S63-S64
Author(s):  
A. K. MUKHOPADHYAY ◽  
H. G. BOHNET
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Leydig Cell ◽  
Kinase C ◽  
Mouse Leydig Cell

scholarly journals Dysregulation of protein kinase C in adult depression and suicide: evidence from postmortem brain studies

2021 ◽  
Author(s):  
Ghanshyam N Pandey ◽  
Anuradha Sharma ◽  
Hooriyah S Rizavi ◽  
Xinguo Ren
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Postmortem Brain ◽  
Cortical Region ◽  
Cytosol Fraction ◽  
Kinase C ◽  
Pkc Isozymes

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region [Brodmann area 9 (BA9)] in 24 normal control (NC) subjects, 24 depressed suicide (DS) subjects and 12 depressed non-suicide (DNS) subjects. The levels of mRNA in the prefrontal cortex (PFC) were determined by qRT-PCR and the protein expression was determined by Western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ and PKCε and decreased protein expression either in the membrane or the cytosol fraction of PKC isozymes - PKCα, PKCβI, PKCβII and PKCδ in DS and DNS subjects compared with NC subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.

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