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.

scholarly journals Targeting Protein Kinase C in Glioblastoma Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 381
Author(s):  
Noelia Geribaldi-Doldán ◽  
Irati Hervás-Corpión ◽  
Ricardo Gómez-Oliva ◽  
Samuel Domínguez-García ◽  
Félix A. Ruiz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Combined Treatment ◽  
Primary Brain Tumor ◽  
Kinase C ◽  
Pkc Isozymes ◽  
New Generation ◽  
Effective Drugs

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.

Regulation of arginine vasopressin mRNA in rat fetal hypothalamic cell culture. Role of protein kinases and glucocorticoids

1993 ◽  
Vol 10 (1) ◽  
pp. 51-57 ◽  
Author(s):  
S-B Hu ◽  
L A Tannahill ◽  
S L Lightman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Protein Kinase A ◽  
Arginine Vasopressin ◽  
In Situ Hybridization Histochemistry ◽  
Kinase C ◽  
Kinase A

ABSTRACT Studies have been performed to investigate the regulation of arginine vasopressin (AVP) mRNA expression in fetal hypothalamic cultures. AVP mRNA-positive neurones were identified by in-situ hybridization histochemistry, and changes in mRNA expression were quantitated by nuclease protection assay. Both protein kinase C and protein kinase A activators increased the expression of AVP mRNA, in contrast to dexamethasone, which inhibited the responses to both protein kinase C and protein kinase A activation.

scholarly journals Protein kinase C isozymes; predictors of progression free survival in NSCLC patients

2019 ◽  
Author(s):  
Ann Rita Halvorsen ◽  
Mads Haugland Haugen ◽  
Åsa Kristina Öjlert ◽  
Marius Lund-Iversen ◽  
Lars Jørgensen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Molecular Subtypes ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Pkc Β ◽  
Low Expression

Abstract Background Protein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and EGFR-, TP53- and KRAS-mutations. Methods We performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using reverse phase protein arrays. Biopsies from 80 patients with operable lung adenocarcinomas were analyzed for protein expression and association with progression free survival (PFS) were studied. Results Spearman rank correlation analysis identified 56 proteins with significant association to PFS (p<0.05). High expression of protein kinase C (PKC)-α and the phosporylated state of PKC-α, PKC-β and PKC-δ, showed the strongest positive correlation to PFS, especially in the wild type samples. This was confirmed in gene expression data from 186 samples. Based on protein expression, unsupervised hierarchical clustering separated the samples into four subclusters enriched with the molecular subtypes TRU, PI or PP (p=0.0001). Subcluster 2 contained a smaller cluster (2a) enriched with samples of the subtype PP, low expression of the PKC isozymes, and associated with poor PFS (p=0.003) compared to the other samples. Subcluster 2a revealed increased expression of neuroendocrine markers, supporting the aggressive behavior. Low expression of the PKC isozymes in the subtype PP and a reduced relapse free survival was confirmed with the TCGA LUAD samples. Conclusion This study identified different proteins associated with PFS depending on molecular subtype, smoking- and mutational-status, with PKC-α, PKC-β and PKC-δ showing the strongest correlation. Cluster analysis detected a subgroup of samples enriched for samples of the PP subtype and poor PFS, which may benefit from a more aggressive treatment regimen.

Protein kinase C regulates endocytosis and recycling of E-cadherin

2002 ◽  
Vol 283 (2) ◽  
pp. C489-C499 ◽  
Author(s):  
Tam Luan Le ◽  
Shannon R. Joseph ◽  
Alpha S. Yap ◽  
Jennifer L. Stow
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Recycling Endosomes ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Pkc Activation ◽  
Darby Canine Kidney ◽  
E Cadherin

E-cadherin is a major component of adherens junctions in epithelial cells. We showed previously that a pool of cell surface E-cadherin is constitutively internalized and recycled back to the surface. In the present study, we investigated the potential role of protein kinase C (PKC) in regulating the trafficking of surface E-cadherin in Madin-Darby canine kidney cells. Using surface biotinylation and immunofluorescence, we found that treatment of cells with phorbol esters increased the rate of endocytosis of E-cadherin, resulting in accumulation of E-cadherin in apically localized early or recycling endosomes. The recycling of E-cadherin back to the surface was also decreased in the presence of phorbol esters. Phorbol ester-induced endocytosis of E-cadherin was blocked by specific inhibitors, implicating novel PKC isozymes, such as PKC-ε in this pathway. PKC activation led to changes in the actin cytoskeleton facilitating E-cadherin endocytosis. Depolymerization of actin increased endocytosis of E-cadherin, whereas the PKC-induced uptake of E-cadherin was blocked by the actin stabilizer jasplakinolide. Our findings show that PKC regulates vital steps of E-cadherin trafficking, its endocytosis, and its recycling.

scholarly journals Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?

2021 ◽  
Author(s):  
Gema Lorden Losada ◽  
Alexandra C Newton
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Spinocerebellar Ataxia Type ◽  
Membrane Phospholipids ◽  
Brain Physiology ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Hydrolysis Of ◽  
The Brain

Protein Kinase C (PKC) isozymes are tightly regulated kinases that transduce a myriad of signals from receptor-mediated hydrolysis of membrane phospholipids. They play an important role in brain physiology, and dysregulation of PKC activity is associated with neurodegeneration. Gain-of-function mutations in PKCα are associated with Alzheimer’s disease and mutations in PKCγ cause spinocerebellar ataxia type 14. This article presents an overview of the role of the conventional PKCα and PKCγ in neurodegeneration and proposes repurposing PKC inhibitors, which failed in clinical trials for cancer, for the treatment of neurodegenerative diseases.

scholarly journals Conventional protein kinase C in the brain: 40 years later

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Julia A. Callender ◽  
Alexandra C. Newton
Keyword(s):  
Cell Death ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Loss Of Function ◽  
Membrane Phospholipids ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Hydrolysis Of ◽  
The Brain

Protein kinase C (PKC) is a family of enzymes whose members transduce a large variety of cellular signals instigated by the receptor-mediated hydrolysis of membrane phospholipids. While PKC has been widely implicated in the pathology of diseases affecting all areas of physiology including cancer, diabetes, and heart disease—it was discovered, and initially characterized, in the brain. PKC plays a key role in controlling the balance between cell survival and cell death. Its loss of function is generally associated with cancer, whereas its enhanced activity is associated with neurodegeneration. This review presents an overview of signaling by diacylglycerol (DG)-dependent PKC isozymes in the brain, and focuses on the role of the Ca2+-sensitive conventional PKC isozymes in neurodegeneration.

Expression of Protein Kinase C Isozymes in Human Basophils: Regulation by Physiological and Nonphysiological Stimuli

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1206-1218 ◽  
Author(s):  
Katsushi Miura ◽  
Donald W. MacGlashan Jr
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Histamine Release ◽  
Membrane Fraction ◽  
Resting Cells ◽  
Cytosol Fraction ◽  
Ige Antibody ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Human Basophils

The expression of protein kinase C (PKC) isozymes in human basophils and the regulation of PKC isozymes during basophil activation by phorbol 12-myristate 13-acetate (PMA) ± ionomycin, f-met-leu-phe (FMLP), and anti-IgE antibody were examined. In human basophils (> 98% purity), PKCβΙ, βΙΙ, δ, and  were expressed, PKC was difficult to detect, and PKCγ and η were undetectable. In unstimulated basophils, PKCβI and βII were found primarily in the cytosol fraction (95% ± 3% of total and 98% ± 1%, respectively). Within 5 minutes of stimulation with PMA (100 ng/mL), both PKCβI and βII were translocated to the membrane fraction (85% ± 4% and 83% ± 6%, respectively). In resting cells, 48% ± 3% and 61% ± 10% of PKCδ and , respectively, existed in the membrane fraction. Within 1 minute of stimulation with PMA, 90% ± 6% of PKC was found in the membrane fraction, however, no translocation of PKCδ was apparent. Stimulation with FMLP caused modest translocation (≈20%) of all PKC isozymes by 1 minute, whereas stimulation with anti-IgE antibody led to no detectable changes in PKC location throughout a 15-minute period of measurement. However, concentrations of PMA and ionomycin that alone caused no PKC translocation and little histamine release, together caused significant histamine release but no apparent PKC translocation. Studies with bis-indolylmaleimide analogs showed inhibition of PMA-induced, but not anti–IgE-induced, histamine release. These pharmacological studies suggest that PKC does not play a prodegranulatory role in human basophil IgE-mediated secretion. © 1998 by The American Society of Hematology.

Expression of Protein Kinase C Isozymes in Human Basophils: Regulation by Physiological and Nonphysiological Stimuli

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1206-1218 ◽  
Author(s):  
Katsushi Miura ◽  
Donald W. MacGlashan Jr
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Histamine Release ◽  
Membrane Fraction ◽  
Resting Cells ◽  
Cytosol Fraction ◽  
Ige Antibody ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Human Basophils

Abstract The expression of protein kinase C (PKC) isozymes in human basophils and the regulation of PKC isozymes during basophil activation by phorbol 12-myristate 13-acetate (PMA) ± ionomycin, f-met-leu-phe (FMLP), and anti-IgE antibody were examined. In human basophils (&gt; 98% purity), PKCβΙ, βΙΙ, δ, and  were expressed, PKC was difficult to detect, and PKCγ and η were undetectable. In unstimulated basophils, PKCβI and βII were found primarily in the cytosol fraction (95% ± 3% of total and 98% ± 1%, respectively). Within 5 minutes of stimulation with PMA (100 ng/mL), both PKCβI and βII were translocated to the membrane fraction (85% ± 4% and 83% ± 6%, respectively). In resting cells, 48% ± 3% and 61% ± 10% of PKCδ and , respectively, existed in the membrane fraction. Within 1 minute of stimulation with PMA, 90% ± 6% of PKC was found in the membrane fraction, however, no translocation of PKCδ was apparent. Stimulation with FMLP caused modest translocation (≈20%) of all PKC isozymes by 1 minute, whereas stimulation with anti-IgE antibody led to no detectable changes in PKC location throughout a 15-minute period of measurement. However, concentrations of PMA and ionomycin that alone caused no PKC translocation and little histamine release, together caused significant histamine release but no apparent PKC translocation. Studies with bis-indolylmaleimide analogs showed inhibition of PMA-induced, but not anti–IgE-induced, histamine release. These pharmacological studies suggest that PKC does not play a prodegranulatory role in human basophil IgE-mediated secretion. © 1998 by The American Society of Hematology.

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