Biologically Active Lipids and Lipid-modulated Protein Kinase in Plants

1996 ◽  
pp. 197-215
Author(s):  
Günther F. E. Scherer
Keyword(s):  
Protein Kinase ◽  
Biologically Active

Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport. Update II

2001 ◽  
Vol 226 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Robert V. Farese
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Intracellular Signaling ◽  
Glucose Transporter ◽  
De Novo ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Cell Types ◽  
Biologically Active

Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidyicholine with subsequent increases in phosphatidic acid (PA) and diacyiglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3 also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.

Enhanced Soluble Production of Biologically Active Recombinant Human p38 Mitogen-Activated-Protein Kinase (MAPK) in Escherichia coli

2007 ◽  
Vol 14 (8) ◽  
pp. 756-760 ◽  
Author(s):  
Sunil K. Khattar ◽  
Pankaj Gulati ◽  
Prabuddha K. Kundu ◽  
Vibhuti Singh ◽  
Usha Bughani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protein Kinase ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

scholarly journals The Immunomodulatory and Anti-Inflammatory Role of Polyphenols

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1618 ◽  
Author(s):  
Nour Yahfoufi ◽  
Nawal Alsadi ◽  
Majed Jambi ◽  
Chantal Matar
Keyword(s):  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Clear Understanding ◽  
Akt Inhibitor ◽  
Amino Terminal ◽  
Anti Inflammatory ◽  
Arachidonic Acids

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.

scholarly journals Regularities of endogenous lipid metabolites formation in phorbol 12-miristate 13-acetate-stimulated peripheral blood lymphocytes at leukemia

2011 ◽  
Vol 57 (4) ◽  
pp. 420-428
Author(s):  
T.B. Batikyan ◽  
G.V. Hakopyan ◽  
M.P. Lazyan ◽  
T.P. Torgomyan ◽  
R.A. Kazaryan ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Palmitic Acid ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Biologically Active ◽  
Leukemic Cells ◽  
Blood Lymphocytes ◽  
Kinase C ◽  
Lipid Metabolites

Regularities of biologically active lipid metabolites formation in dynamics (5, 10, 30, 60 s) by phorbol 12-miristate 13-acetate stimulation in [14C]palmitic acid have been investigated in normal and leukemia peripheral blood lymphocytes prelabeled with [14C]palmitate. In normal cells there was two-phase formation of 1,2-diacylglycerol (5, 30 s), lysophosphatidylcholine (10, 60 s), as well as free palmitic acid at 10 s of stimulation. Under the identical experimental conditions there was inhibition of investigated lipid release processes at early (5 and 10 s) stages of stimulation of leukemic lymphocytes. At later (30, 60 s) terms of these lymphocytes the activation, basically, similar to norm changes in the formation of palmitic acid-containing metabolites except free palmitic acid (the level of which raised only at 60 second of the post-stimulation) was found. Various protein kinases C are involved in the regulation of investigated lipid levels at certain stages of signal transduction both in norm, and in blast cells. Short-term (5, 10 s) activations of healthy donors lymphocytes are coupled to functioning of Са2+-independent isoforms of protein kinase C. The inhibition of this protein kinase C in leukemic cells leads to normalization of the investigated lipid release. The data obtained suggests disorders of early membrane-bound reactions in agonist - and a protein kinase C-mediated processes of formation palmitic acid-containing lipid metabolites in the leukemic cells in comparison with the norm.

scholarly journals The PI3k/Akt Pathway Is Associated With Angiogenesis, Oxidative Stress and Survival of Mesenchymal Stem Cells in Pathophysiologic Condition in Ischemia

2019 ◽  
pp. S131-S138 ◽  
Author(s):  
A. SAMAKOVA ◽  
A. GAZOVA ◽  
N. SABOVA ◽  
S. VALASKOVA ◽  
M. JURIKOVA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biologically Active ◽  
Akt Pathway ◽  
First Choice ◽  
Ischemic Diseases

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

Phorbol amplification of serotonin-induced arterial contractions is endothelium dependent

1989 ◽  
Vol 257 (4) ◽  
pp. H1174-H1179 ◽  
Author(s):  
P. M. Consigny
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Sodium Nitroprusside ◽  
Dimethyl Sulfoxide ◽  
Abdominal Aorta ◽  
Biologically Active ◽  
Relaxing Factor ◽  
Kinase C ◽  
Endothelium Derived Relaxing Factor

This study determined the effect of phorbol pretreatment on serotonin [5-hydroxytryptamine (5-HT)]-induced contractions of rabbit abdominal aorta. Rings of aorta pretreated with 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-7) M) contracted more strongly (P less than 0.01) than rings pretreated with the vehicle dimethyl sulfoxide (0.0007%), but only at low 5-HT concentrations (10(-8) to 10(-7) M). A 10-min exposure to TPA (10(-7) M) increased (P less than 0.01) 5-HT contractions (10(-7) M) from 23.7 +/- 2.6 to 42.1 +/- 4.5%. This amplification required an intact endothelium and the use of a biologically active phorbol. Pretreatment with TPA (10(-7) M) reduced (P less than 0.01) acetylcholine-induced relaxations from 56.6 +/- 6.6 to 20.0 +/- 13.8%. Changes in guanosine 3',5'-cyclic monophosphate-mediated relaxation are not involved in this decrease, since relaxations to sodium nitroprusside (10(-9) to 10(-8) M) were not altered by TPA pretreatment. These results suggest that activation of protein kinase C in endothelial cells may produce arterial supersensitivity to 5-HT by decreasing the release of endothelium-derived relaxing factor(s) and/or by increasing the release of endothelium-derived contracting factor(s).

Regulation of Na+-H+ exchange in normal NIH-3T3 cells and in NIH-3T3 cells expressing the ras oncogene

1989 ◽  
Vol 256 (4) ◽  
pp. C756-C763 ◽  
Author(s):  
N. E. Owen ◽  
J. Knapik ◽  
F. Strebel ◽  
W. G. Tarpley ◽  
R. R. Gorman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Inositol Trisphosphate ◽  
Biologically Active ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
Calmodulin Antagonist ◽  
Kinase C ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Our laboratory and others have demonstrated that Na+-H+ exchange can be regulated by two different pathways; one that is mediated by an inositol trisphosphate-stimulated increase in intracellular calcium activity, and one that is mediated by an increase in protein kinase C activity. To determine whether one of these pathways is more important than the other, or whether one pathway is physiologically relevant, we employed normal NIH-3T3 cells (3T3 cells) and NIH-3T3 cells expressing the EJ human bladder ras oncogene (EJ cells). The EJ cells were chosen because they provide a genetic model that does not exhibit serum- or platelet-derived growth factor (PDGF)-stimulated inositol trisphosphate release or Ca2+ mobilization. It was found that serum- or PDGF-stimulated Na+-H+ exchange was more pronounced in EJ cells than in control 3T3 cells. As expected, serum- or PDGF-stimulated Na+-H+ exchange in 3T3 cells was inhibited by chelating intracellular Ca2+ with the intracellular Ca2+ chelator quin2, by the intracellular Ca2+ antagonist 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), and by the calmodulin antagonist trifluoperazine. In contrast, these agents did not inhibit serum- or PDGF-stimulated Na+-H+ exchange in EJ cells. Activators of protein kinase C (e.g., 1-oleoyl-2-acetylglycerol or biologically active phorbol esters) were found to stimulate Na+-H+ exchange in EJ cells to the same extent as serum. However, these agents were considerably less effective than serum in control 3T3 cells. Despite these findings, PDGF did not stimulate diacylglycerol levels in EJ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Augmentation of c-fos mRNA expression by activators of protein kinase C in fresh, terminally differentiated resting macrophages.

1987 ◽  
Vol 7 (2) ◽  
pp. 595-599 ◽  
Author(s):  
D Radzioch ◽  
B Bottazzi ◽  
L Varesio
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Ionophore ◽  
Peritoneal Macrophages ◽  
Biologically Active ◽  
Specific Response ◽  
Tumoricidal Activity ◽  
Differentiated Cells ◽  
Kinase C ◽  
Protein Kinase C Activation

Expression of c-fos mRNA was investigated in fresh, normal peritoneal macrophages (M phi), which are terminally differentiated, nonproliferating cells. The levels of c-fos mRNA were dramatically increased by stimulation with phorbol myristate acetate (PMA), calcium ionophore, or 1-oleoyl-2-acetoyl glycerol (OAG). Induction of c-fos mRNA by all the above agents followed similar kinetics, with a peak of mRNA 30 min after stimulation. These results demonstrate that c-fos mRNA can be augmented in fresh, terminally differentiated cells. Since the stimuli increasing c-fos mRNA are direct or indirect activators of protein kinase C, our data suggest that in M phi c-fos mRNA is controlled by protein kinase C activation. PMA, calcium ionophore, and OAG were biologically active in M phi. PMA and calcium ionophore induced respiratory burst and tumoricidal activity, respectively, whereas OAG and PMA were chemotactic for M phi. Interferons beta and gamma, potent M phi activators eliciting tumoricidal activity, did not alter the levels of c-fos mRNA. These results indicate that c-fos mRNA augmentation is a stimulus-specific rather than a function-specific response connected to activation of protein kinase C.

scholarly journals Mechanism of Human Immunodeficiency Virus-Induced Complement Expression in Astrocytes and Neurons

2002 ◽  
Vol 76 (7) ◽  
pp. 3179-3188 ◽  
Author(s):  
Cornelia Speth ◽  
Thomas Schabetsberger ◽  
Iradji Mohsenipour ◽  
Gabriele Stöckl ◽  
Reinhard Würzner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Neutralizing Antibodies ◽  
Prolonged Exposure ◽  
Biologically Active ◽  
Complement Factor ◽  
Kinase C ◽  
Immunodeficiency Virus ◽  
The Brain

ABSTRACT The cerebral complement system is hypothesized to contribute to neurodegeneration in the pathogenesis of AIDS-associated neurological disorders. Our former results have shown that the human immunodeficiency virus (HIV) strongly induces the synthesis of complement factor C3 in astrocytes. This upregulation explains in vivo data showing elevated complement levels in the cerebrospinal fluid of patients with AIDS-associated neurological symptoms. Since inhibition of complement synthesis and activation in the brain may represent a putative therapeutic goal to prevent virus-induced damage, we analyzed in detail the mechanisms of HIV-induced modulation of C3 expression. HIV-1 increased the C3 levels in astrocyte culture supernatants from 30 to up to 400 ng/ml; signal transduction studies revealed that adenylate cyclase activation with upregulation of cyclic AMP is the central signaling pathway to mediate that increase. Furthermore, activity of protein kinase C is necessary for HIV induction of C3, since inhibition of protein kinase C by prolonged exposure to the phorbol ester tetradecanoyl phorbol acetate partly abolished the HIV effect. The cytokines tumor necrosis factor alpha and gamma interferon were not involved in mediating the HIV-induced C3 upregulation, since neutralizing antibodies had no effect. Besides whole HIV virions, the purified viral proteins Nef and gp41 are biologically active in upregulating C3, whereas Tat, gp120, and gp160 were not able to modulate C3 synthesis. Further experiments revealed that neurons were also able to respond on incubation with HIV with increased C3 synthesis, although the precise pattern was slightly different from that in astrocytes. This strengthens the hypothesis that HIV-induced complement synthesis represents an important mechanism for the pathogenesis of AIDS in the brain.

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