Corrections: 12(S)-Hydroxyeicosatetraenoic Acid and 13(S)- Hydroxyoctadecadienoic Acid Regulation of Protein Kinase C-  in Melanoma Cells: Role of Receptor-Mediated Hydrolysis of Inositol Phospholipids

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.

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Conventional protein kinase C in the brain: 40 years later

Neuronal Signaling ◽

10.1042/ns20160005 ◽

2017 ◽

Vol 1 (2) ◽

Cited By ~ 15

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.

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Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids

Blood ◽

10.1182/blood.v72.2.491.bloodjournal722491 ◽

1988 ◽

Vol 72 (2) ◽

pp. 491-499 ◽

Cited By ~ 1

Author(s):

DM Shasby ◽

M Yorek ◽

SS Shasby

Keyword(s):

Fatty Acids ◽

Endothelial Cells ◽

Protein Kinase C ◽

Endothelial Cell ◽

Protein Kinase ◽

Phospholipase C ◽

Inflammatory Cells ◽

Kinase C ◽

Inositol Phospholipids ◽

Hydrolysis Of

Oxidants released from inflammatory cells contribute to the pathogenesis of acute inflammatory edema in many models. Chemically produced oxidants can reversibly alter the barrier properties of cultured endothelial and epithelial monolayers. This report examines the effects of nonlytic doses of H2O2 on endothelial cell lipids. H2O2 oxidized omega-6 fatty acids in the endothelial cells and initiated hydrolysis of endothelial cell phospholipids. When endothelial cells were exposed to peroxidized linoleic acid, it caused lysis of the cells at doses 1,000-fold lower than effective doses of H2O2. The phospholipid hydrolysis was directed primarily at the inositol phospholipids and consisted of both A and C type phospholipase activity. The phospholipase A hydrolysis resulted in increases in endothelial cell free fatty acids and lysophosphatidylinositol. The phospholipase C hydrolysis resulted in increases in diglycerides, phosphatidic acid, and inositol polyphosphate levels. The phospholipase C hydrolysis of phosphatidylinositol is known to activate protein kinase C in most cells. Stimulation of protein kinase C with phorbol- 12,13-dibutyrate increased albumin flux across endothelial monolayers and altered endothelial cell shape, similar to effects of oxidants. These data are consistent with the hypothesis that oxidant-initiated hydrolysis of endothelial cell inositol phospholipids contributes to oxidant-mediated reversible changes in endothelial monolayer barrier function.

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Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids

Blood ◽

10.1182/blood.v72.2.491.491 ◽

1988 ◽

Vol 72 (2) ◽

pp. 491-499 ◽

Cited By ~ 71

Author(s):

DM Shasby ◽

M Yorek ◽

SS Shasby

Keyword(s):

Fatty Acids ◽

Endothelial Cells ◽

Protein Kinase C ◽

Endothelial Cell ◽

Protein Kinase ◽

Phospholipase C ◽

Inflammatory Cells ◽

Kinase C ◽

Inositol Phospholipids ◽

Hydrolysis Of

Abstract Oxidants released from inflammatory cells contribute to the pathogenesis of acute inflammatory edema in many models. Chemically produced oxidants can reversibly alter the barrier properties of cultured endothelial and epithelial monolayers. This report examines the effects of nonlytic doses of H2O2 on endothelial cell lipids. H2O2 oxidized omega-6 fatty acids in the endothelial cells and initiated hydrolysis of endothelial cell phospholipids. When endothelial cells were exposed to peroxidized linoleic acid, it caused lysis of the cells at doses 1,000-fold lower than effective doses of H2O2. The phospholipid hydrolysis was directed primarily at the inositol phospholipids and consisted of both A and C type phospholipase activity. The phospholipase A hydrolysis resulted in increases in endothelial cell free fatty acids and lysophosphatidylinositol. The phospholipase C hydrolysis resulted in increases in diglycerides, phosphatidic acid, and inositol polyphosphate levels. The phospholipase C hydrolysis of phosphatidylinositol is known to activate protein kinase C in most cells. Stimulation of protein kinase C with phorbol- 12,13-dibutyrate increased albumin flux across endothelial monolayers and altered endothelial cell shape, similar to effects of oxidants. These data are consistent with the hypothesis that oxidant-initiated hydrolysis of endothelial cell inositol phospholipids contributes to oxidant-mediated reversible changes in endothelial monolayer barrier function.

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

Acta Endocrinologica ◽

10.1530/acta.0.111s063 ◽

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

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

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyab003 ◽

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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