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Cell Calcium Jun 2009Stimulation of receptor-operated (ROCs) and store-operated (SOCs) Ca(2+)-permeable cation channels by vasoconstrictors has many important physiological functions in... (Review)
Review
Stimulation of receptor-operated (ROCs) and store-operated (SOCs) Ca(2+)-permeable cation channels by vasoconstrictors has many important physiological functions in vascular smooth muscle. The present review indicates that ROCs and SOCs with diverse properties in different blood vessels are likely to be explained by composition of different subunits from the canonical transient receptor potential (TRPC) family of cation channel proteins. In addition we illustrate that activation of native TRPC ROCs and SOCs involves different phospholipase-mediated transduction pathways linked to generation of diacylglycerol (DAG). Moreover we describe recent novel data showing that the endogenous phospholipid phosphoinositol 4,5-bisphosphate (PIP(2)) has profound and contrasting actions on TRPC ROCs and SOCs. Optimal activation of a native TRPC6 ROC by angiotensin II (Ang II) requires both depletion of PIP(2) and generation of DAG which leads to stimulation of TRPC6 via a PKC-independent mechanism. The data also indicate that PIP(2) has a marked constitutive inhibitory action of TRPC6 and DAG and PIP(2) are physiological antagonists on TRPC6 ROCs. In contrast PIP(2) stimulates TRPC1 SOCs and has an obligatory role in activation of these channels by store-depletion which requires PKC-dependent phosphorylation of TRPC1 proteins. Finally, we conclude that interactions between PIP(2) bound to TRPC proteins at rest, generation of DAG and PKC-dependent phosphorylation of TRPC proteins have a fundamental role in activation mechanisms of ROCs and SOCs in vascular smooth muscle.
Topics: Calcium; Diglycerides; Muscle, Smooth, Vascular; Phosphatidylinositol 4,5-Diphosphate; Signal Transduction; Transient Receptor Potential Channels
PubMed: 19324408
DOI: 10.1016/j.ceca.2009.02.007 -
Bioscience Reports May 1987Measurements of intracellular Ca2+ in adrenal medullary cells suggest that a transient rise in Ca2+ leads to a transient secretory response, the rise in Ca2+ being... (Review)
Review
Measurements of intracellular Ca2+ in adrenal medullary cells suggest that a transient rise in Ca2+ leads to a transient secretory response, the rise in Ca2+ being brought about by an influx through voltage-sensitive Ca channels which subsequently inactivate. The level of Ca2+ observed is much smaller than the Ca2+ needed to trigger secretion when introduced directly into the cell. The discrepancy is removed by the presence of diacylglycerol, which increases the sensitivity of the secretory process to Ca2+. The site of action of Ca2+ and diacylglycerol is probably protein kinase C, and the different secretory responses to increases of Ca2+ and diacylglycerol can be modelled in terms of a preferential order of binding of these two substrates to the enzyme. ATP is needed for secretion: one role is possibly to confer stability to the secretory apparatus; another may involve phosphorylation of some key protein. The kinetics of secretion suggest that if Ca2+ regulates phosphorylation or dephosphorylation, then it is the rate of change of phosphorylation that controls secretion rather than the extent of phosphorylation or dephosphorylation. Guanine nucleotide-binding proteins may play a role not only at the level of signal transduction coupling, but also at or near the site of exocytosis, and the mechanism by which some Botulinum toxins inhibit secretion may be associated with these proteins.
Topics: Adrenal Glands; Animals; Calcium; Cattle; Diglycerides; Glycerides
PubMed: 3315029
DOI: 10.1007/BF01362500 -
FEBS Letters May 2015Diacylglycerol kinase (DGK) η plays important roles in various patho-physiological events such as oncogenesis. In this study, we performed an enzymological...
Diacylglycerol kinase (DGK) η plays important roles in various patho-physiological events such as oncogenesis. In this study, we performed an enzymological characterization of DGKη splice variant 1 (DGKη1). The Km value for diacylglycerol was 0.14 mol%. Intriguingly, the Km value of DGKη1 for diacylglycerol was at least 9-fold lower than those of other DGK isozymes including DGKα, indicating that DGKη1 is a high affinity isozyme for diacylglycerol. Therefore, DGKη1 is a unique DGK isozyme, which may function at particular membrane sites where only low concentrations of diacylglycerol are supplied.
Topics: Animals; Diacylglycerol Kinase; Diglycerides; Humans; Isoenzymes; Swine
PubMed: 25862496
DOI: 10.1016/j.febslet.2015.03.032 -
Biochimica Et Biophysica Acta.... Nov 2017The glycerophospholipids phosphatidylethanolamine, phosphatidylglycerol (PG), and cardiolipin (CL) are major structural components of bacterial membranes. In some... (Review)
Review
The glycerophospholipids phosphatidylethanolamine, phosphatidylglycerol (PG), and cardiolipin (CL) are major structural components of bacterial membranes. In some bacteria, phosphatidylcholine or phosphatidylinositol and its derivatives form part of the membrane. PG or CL can be modified with the amino acid residues lysine, alanine, or arginine. Diacylglycerol is the lipid anchor from which syntheses of phosphorus-free glycerolipids, such as glycolipids, sulfolipids, or homoserine-derived lipids initiate. Many membrane lipids are subject to turnover and some of them are recycled. Other lipids associated with the membrane include isoprenoids and their derivatives such as hopanoids. Ornithine-containing lipids are widespread in Bacteria but absent in Archaea and Eukarya. Some lipids are probably associated exclusively with the outer membrane of many bacteria, i.e. lipopolysaccharides, sphingolipids, or sulfonolipids. For certain specialized membrane functions, specific lipid structures might be required. Upon cyst formation in Azotobacter vinelandii, phenolic lipids are accumulated in the membrane. Anammox bacteria contain ladderane lipids in the membrane surrounding the anammoxosome organelle, presumably to impede the passage of highly toxic compounds generated during the anammox reaction. Considering that present knowledge on bacterial lipids was obtained from only a few bacterial species, we are probably only starting to unravel the full scale of lipid diversity in bacteria. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.
Topics: Bacteria; Diglycerides; Glycerophospholipids; Lipogenesis; Membrane Lipids; Molecular Structure; Structure-Activity Relationship
PubMed: 27760387
DOI: 10.1016/j.bbalip.2016.10.007 -
The Journal of Nutrition Jun 1995Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular binding site of the phorbol... (Review)
Review
Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular binding site of the phorbol ester tumor promoters, protein kinase C (PKC). High-fat diets increase the activity of PKC but have no impact on the steady-state protein levels. Energy restriction reduces the activity of PKC, presumably through reduction in the steady-state levels of particular isoenzymes (PKC alpha and PKC zeta). Phorbol-binding studies with epidermal cells from mice fed energy-restricted diets indicated a reduction of phorbol-binding sites in these cells. Investigations into lipid metabolism showed that both dietary fat and energy restriction increased epidermal cell diacylglycerol (DAG). The increase in DAG in cells from energy-restricted mice may be due to increased turnover of phosphatidylinositol, as was evident in the reduced phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-biphosphate and elevated inositol biphosphate and inositol triphosphate in these cells.
Topics: Animals; Dietary Fats; Diglycerides; Energy Intake; Humans; Phorbol Esters; Protein Kinase C; Skin; Skin Neoplasms
PubMed: 7782924
DOI: 10.1093/jn/125.suppl_6.1673S -
Molecules (Basel, Switzerland) May 2021Herein, we prepared 1,3-dipalmitoyl-2-oleoyl glycerol (POP)-rich fats with reduced levels of diacylglycerols (DAGs), adversely affecting the tempering of chocolate, via...
Herein, we prepared 1,3-dipalmitoyl-2-oleoyl glycerol (POP)-rich fats with reduced levels of diacylglycerols (DAGs), adversely affecting the tempering of chocolate, via two-step hexane fractionation of palm stearin. DAG content in the as-prepared fats was lower than that in POP-rich fats obtained by previously reported conventional two-step acetone fractionation. Cocoa butter equivalents (CBEs) were fabricated by blending the as-prepared fats with 1,3-distearoyl-2-oleoyl glycerol (SOS)-rich fats obtained by hexane fractionation of degummed shea butter. POP-rich fats achieved under the best conditions for the fractionation of palm stearin had a significantly lower DAG content (1.6 %) than that in the counterpart (4.6 %) prepared by the previously reported method. The CBEs fabricated by blending the POP- and SOS-rich fats in a weight ratio of 40:60 contained 63.7 % total symmetric monounsaturated triacylglycerols, including 22.0 % POP, 8.6 % palmitoyl-2-oleoyl-3-stearoyl--glycerol, 33.1 % SOS, and 1.3 % DAGs, which was not substantially different from the DAG content in cocoa butter (1.1 %). Based on the solid-fat content results, it was concluded that, when these CBEs were used for chocolate manufacture, they blended with cocoa butter at levels up to 40 %, without distinctively altering the hardness and melting behavior of cocoa butter.
Topics: Cacao; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; Dietary Fats; Diglycerides; Fatty Acids; Glycerol; Hexanes; Palm Oil; Plant Oils; Temperature; Triglycerides
PubMed: 34072180
DOI: 10.3390/molecules26113231 -
ELife Jun 2022Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation...
Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly, and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria-vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation.
Topics: Animals; Diglycerides; Homeostasis; Lipid Metabolism; Mice; Saccharomyces cerevisiae; Triglycerides
PubMed: 35766356
DOI: 10.7554/eLife.77665 -
Biochemistry May 2017Conserved homology-1 (C1) domains are peripheral membrane domains that target their host proteins to diacylglycerol (DAG)-containing membranes. It has been previously...
Conserved homology-1 (C1) domains are peripheral membrane domains that target their host proteins to diacylglycerol (DAG)-containing membranes. It has been previously shown that a conservative aromatic mutation of a single residue in the C1 domain has a profound effect on DAG affinity. We report that the "DAG-toggling" mutation changes the conformational dynamics of the loop region that forms the binding site for the C1 activators. Moreover, there is a correlation among the residue identity at the mutation site, DAG affinity, and loop dynamics in four C1 variants. We propose that "toggling" of DAG affinity may occur through modulation of both protein-membrane interactions and the geometry of the activator-binding cleft, with the loop dynamics being responsible for the latter.
Topics: Diglycerides; Models, Molecular; Protein Conformation; Protein Kinase C; Thermodynamics
PubMed: 28505428
DOI: 10.1021/acs.biochem.7b00228 -
EMBO Reports Apr 2005Meeting on Molecular Advances in Diacylglycerol Signalling (Review)
Review
Meeting on Molecular Advances in Diacylglycerol Signalling
Topics: Diglycerides; Models, Biological; Neoplasms; Nervous System; Protein Binding; Protein Kinase C; Protein Structure, Tertiary; Signal Transduction
PubMed: 15791268
DOI: 10.1038/sj.embor.7400378 -
Food Chemistry May 2020Formation of foams is critical for tailoring the texture and mouthfeel of fat-based products. Diacylglycerol (DAG) is regarded as a preferable alternative structurant to...
Formation of foams is critical for tailoring the texture and mouthfeel of fat-based products. Diacylglycerol (DAG) is regarded as a preferable alternative structurant to hydrogenated lipid. Effect of DAG concentration (2-10 wt%) on the characteristics of oleogels and foams including crystal polymorphisms, size and distribution, rheological and thermodynamic properties was investigated. Oleogel prepared with 10 wt% DAG had comparable whipping and foaming stability to that of 6 wt% fully hydrogenated palm oil (FHPO). DAG formed small plate-crystals which tend to occur at the bubble surface, whereas FHPO showed needle-like crystals that were formed mainly in the continuous phase. For the 2 wt% FHPO-8 wt% DAG-based oil foams, interfacial templating crystallization effect contributed to the smaller bubble size and improved rheological properties whereby less oil drainage and foam breakdown occurred. Hence, the non-aqueous foam formed by DAG has broad application prospect because of the thermoresponsive properties and the desirable health benefits.
Topics: Aerosols; Crystallization; Diglycerides; Organic Chemicals
PubMed: 31884300
DOI: 10.1016/j.foodchem.2019.126047