Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular species of diacylglycerol and alkylacylglycerol of Madin-Darby canine Kidney (MDCK) cells were analyzed to determine the sources of diradylglycerols generated during cell growth and phorbol ester stimulation. MDCK cells in log phase growth contained higher levels of diacylglycerol and alkylacylglycerol than confluent cells. Both subclasses of diradylglycerol showed higher levels of saturated and monoenoic species during log phase. Glycerol incorporation into diradylglycerols was increased during growth, consistent with an increase in their synthesis de novo. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, caused an increase in the level of diacylglycerol but not alkylacylglycerol. Log phase MDCK cells showed a greater response to TPA treatment than confluent cells. The molecular species of diacylglycerol generated during stimulation with either TPA or dioctanoylglycerol closely resembled the species of phosphatidylcholine. These results indicate that TPA and synthetic diacylglycerol stimulate endogenous diacylglycerol production through the hydrolysis of phosphatidylcholine. In contrast, the higher content of diacylglycerol and alkylacylglycerol in replicating MDCK cells is the result of an increase in their synthesis de novo.
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PMID:Sources of diradylglycerols generated during cell growth and phorbol ester stimulation in Madin-Darby canine kidney cells. 189 79

We previously suggested that insulin increases diacylglycerol (DAG) in BC3H-1 myocytes, both by increases in synthesis de novo of phosphatidic acid (PA) and by hydrolysis of non-inositol-containing phospholipids, such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). We have now evaluated these insulin effects more thoroughly, and several potential mechanisms for their induction. In studies of the effect on PA synthesis de novo, insulin stimulated [2-3H]glycerol incorporation into PA, DAG, PC/PE and total glycerolipids of BC3H-1 myocytes, regardless of whether insulin was added simultaneously with, or after 2 h or 3 or 10 days of prelabelling with, [2-3H]glycerol. In prelabelled cells, time-related changes in [2-3H]glycerol labelling of DAG correlated well with increases in DAG content: both were maximal in 30-60 s and persisted for 20-30 min. [2-3H]Glycerol labelling of glycerol 3-phosphate, on the other hand, was decreased by insulin, presumably reflecting increased utilization for PA synthesis. Glycerol 3-phosphate concentrations were 0.36 and 0.38 mM before and 1 min after insulin treatment, and insulin effects could not be explained by increases in glycerol 3-phosphate specific radioactivity. In addition to that of [2-3H]glycerol, insulin increased [U-14C]glucose and [1,2,3-3H]glycerol incorporation into DAG and other glycerolipids. Effects of insulin on [2-3H]glycerol incorporation into DAG and other glycerolipids were half-maximal and maximal at 2 nM- and 20 nM-insulin respectively, and were not dependent on glucose concentration in the medium, extracellular Ca2+ or protein synthesis. Despite good correlation between [3H]DAG and DAG content, calculated increases in DAG content from glycerol 3-phosphate specific radioactivity (i.e. via the pathway of PA synthesis de novo) could account for only 15-30% of the observed increases in DAG content. In addition to increases in [3H]glycerol labelling of PC/PE, insulin rapidly (within 30 s) increased PC/PE labelling by [3H]arachidonic acid, [3H]myristic acid, and [14C]choline. Phenylephrine, ionophore A23187 and phorbol esters did not increase [2-3H]glycerol incorporation into DAG or other glycerolipids in 2-h-prelabelling experiments; thus activation of the phospholipase C which hydrolyses phosphatidylinositol, its mono- and bis-phosphate, Ca2+ mobilization, and protein kinase C activation, appear to be ruled out as mechanisms to explain the insulin effect on synthesis de novo of PA, DAG and PC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes. 314 71

The yeast Saccharomyces cerevisiae (baker's yeast or budding yeast) is an excellent eukaryotic model system for cellular biology with a well-explored, completely sequenced genome. Yeast cells possess robust systems for osmotic adaptation. Central to the response to high osmolarity is the HOG pathway, one of the best-explored MAP kinase pathways. This pathway controls via different transcription factors the expression of more than 150 genes. In addition, osmotic responses are also controlled by protein kinase A via a general stress response pathway and by presently unknown signaling systems. The HOG pathway partially controls expression of genes encoding enzymes in glycerol production. Glycerol is the main yeast osmolyte, and its production is essential for growth in a high osmolarity medium. Upon hypo-osmotic shock, yeast cells transiently stimulate another MAP kinase pathway, the so-called PKC pathway, which appears to orchestrate the assembly of the cell surface and the cell wall. In addition, yeast cells show signs of a regulated volume decrease by rapidly exporting glycerol through Fps1p. This unusual MIP channel is gated by osmotic changes and thereby plays a key role in controlling the intracellular osmolyte content. Yeast cells also possess two aquaporins, Aqy1p and Aqy2p. The production of both proteins is strictly regulated, suggesting that these water channels play very specific roles in yeast physiology. Aqy1p appears to be developmentally regulated. Given the strong yeast research community and the excellent tools of genetics and functional genomics available, we expect yeast to be the best-explored cellular organism for several years ahead, and osmotic responses are a focus of interest for numerous yeast researchers.
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PMID:Osmotic adaptation in yeast--control of the yeast osmolyte system. 1195 27

The mechanisms of the impairment in hepatic glucose metabolism induced by free fatty acids (FFAs) and the importance of FFA oxidation in these mechanisms remain unclear. FFA-induced peripheral insulin resistance has been linked to membrane translocation of novel protein kinase C (PKC) isoforms, but the role of PKC in hepatic insulin resistance has not been assessed. To investigate the biochemical pathways that are induced by FFA in the liver and their relation to glucose metabolism in vivo, we determined endogenous glucose production (EGP), the hepatic content of citrate (product of acetyl-CoA derived from FFA oxidation and oxaloacetate), and hepatic PKC isoform translocation after 2 and 7 h Intralipid + heparin (IH) or SAL in rats. Experiments were performed in the basal state and during hyperinsulinemic clamps (insulin infusion rate, 5 mU. kg(-1). min(-1)). IH increased EGP in the basal state (P < 0.001) and during hyperinsulinemia (P < 0.001) at 2 and 7 h. Also, 7-h infusion of IH induced resistance to the suppressive effect of insulin on EGP (P < 0.05). Glycerol infusion (resulting in plasma glycerol levels similar to IH infusion) did not have any effect on EGP. IH increased hepatic citrate content by twofold, independent of the insulin levels and the duration of IH infusion. IH induced hepatic PKC-delta translocation from the cytosolic to membrane fraction in all groups. PKC-delta translocation was greater at 7 compared with 2 h (P < 0.05). In conclusion, 1) increased FFA oxidation may contribute to the FFA-induced increase in EGP in the basal state and during hyperinsulinemia but is not associated with FFA-induced hepatic insulin resistance, and 2) the progressive insulin resistance induced by FFA in the liver is associated with a progressive increase in hepatic PKC-delta translocation.
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PMID:Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta. 1221 85

The effect of substances extracted from Toona sinensis leaves with 50% alcohol solution on lipolysis was investigated in cultured 3T3-L1 differentiated adipocytes. The amount of glycerol released from cells into culture medium was used to measure lipolysis activity. Glycerol release was increased by Toona sinensis leaf extract in a dose-dependent and time-dependent manner. Following treatment of 3T3-L1 adipocyte cells with various concentrations of Toona sinensis leaf extract (0.001, 0.01, and 0.1 mg/mL) for 6 hours, the amounts of glycerol released from 3T3-L1 cells increased from a control value of 99 nmol/mg protein to 127, 144, and 154 nmol/mg protein, respectively. The lipolytic effect of Toona sinensis leaf extract was not inhibited by pretreatment of cells with cycloheximide, econazole, baicalein, or indomethacin. However, the lipolytic activity induced by Toona sinensis leaf extract was diminished by dibutyryl cyclic adenosine-5'-monophosphate (dibutyryl cAMP) and the protein kinase C inhibitor calphostin C. These results indicate that the lipolytic effect induced by Toona sinensis leaf substances may be involved in the protein kinase C pathway and may be down-regulated by cAMP.
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PMID:Effects of Toona sinensis leaf extract on lipolysis in differentiated 3T3-L1 adipocytes. 1296 25

Green tea catechins have been shown to attenuate obesity in animals and humans. The catechins activate adenosine monophosphate-activated protein kinase (AMPK), and thereby increase fatty acid oxidation in liver and skeletal muscles. Green tea catechins have also been shown to reduce body fat in humans. However, the effect of the catechins on lipolysis in adipose tissue has not been fully understood. The aim of this study was to clarify the effect of green tea catechins on lipolysis in adipocytes and to elucidate the underlying mechanism. Differentiated mouse adipocyte cell line (3T3-L1) was stimulated with green tea catechins in the presence or absence of norepinephrine. Glycerol and free fatty acids in the media were measured. Phosphorylation of hormone-sensitive lipase (HSL) was determined by Western blotting, and the mRNA expression levels of HSL, adipose triglyceride lipase (ATGL), and perilipin were determined by quantitative RT-PCR. The cells were treated with inhibitors of protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG), or mitogen-activated protein kinase (MAPK) to determine the responsible pathway. Treatment of 3T3-L1 adipocytes with green tea catechins increased the level of glycerol and free fatty acids released into the media in the presence, but not absence, of norepinephrine, and increased the level of phosphorylated HSL in the cells. The catechins also increased mRNA and protein levels of HSL and ATGL. PKA inhibitor (H89) attenuated the catechin-induced increase in glycerol release and HSL phosphorylation. The results demonstrate that green tea catechins enhance lipolysis in the presence of norepinephrine via a PKA-dependent pathway in 3T3-L1 adipocytes, providing a potential mechanism by which green tea catechins could reduce body fat.
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PMID:Green tea catechins enhance norepinephrine-induced lipolysis via a protein kinase A-dependent pathway in adipocytes. 2584 90

Glycerol-based ether lipids including ether phospholipids form a specialized branch of lipids that in mammals require peroxisomes for their biosynthesis. They are major components of biological membranes and one particular subgroup, the plasmalogens, is widely regarded as a cellular antioxidant. Their vast potential to influence signal transduction pathways is less well known. Here, we summarize the literature showing associations with essential signaling cascades for a wide variety of ether lipids, including platelet-activating factor, alkylglycerols, ether-linked lysophosphatidic acid and plasmalogen-derived polyunsaturated fatty acids. The available experimental evidence demonstrates links to several common players like protein kinase C, peroxisome proliferator-activated receptors or mitogen-activated protein kinases. Furthermore, ether lipid levels have repeatedly been connected to some of the most abundant neurological diseases, particularly Alzheimer's disease and more recently also neurodevelopmental disorders like autism. Thus, we critically discuss the potential role of these compounds in the etiology and pathophysiology of these diseases with an emphasis on signaling processes. Finally, we review the emerging interest in plasmalogens as treatment target in neurological diseases, assessing available data and highlighting future perspectives. Although many aspects of ether lipid involvement in cellular signaling identified in vitro still have to be confirmed in vivo, the compiled data show many intriguing properties and contributions of these lipids to health and disease that will trigger further research.
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PMID:Plasmalogens, platelet-activating factor and beyond - Ether lipids in signaling and neurodegeneration. 3286 63