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Nature Mar 1990
Topics: Animals; Calcium Channels; Diglycerides; Glycerides; Islets of Langerhans; Rats
PubMed: 2156168
DOI: 10.1038/344300c0 -
Annual Review of Biochemistry 1987
Review
Topics: Animals; Calcium; Diglycerides; Glycerides; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Protein Kinase C; Sugar Phosphates
PubMed: 3304132
DOI: 10.1146/annurev.bi.56.070187.001111 -
Nature Reviews. Cancer Apr 2007Almost three decades after the discovery of protein kinase C (PKC), we still have only a partial understanding of how this family of serine/threonine kinases is involved... (Review)
Review
Almost three decades after the discovery of protein kinase C (PKC), we still have only a partial understanding of how this family of serine/threonine kinases is involved in tumour promotion. PKC isozymes - effectors of diacylglycerol (DAG) and the main targets of phorbol-ester tumour promoters - have important roles in cell-cycle regulation, cellular survival, malignant transformation and apoptosis. How do PKC isozymes regulate these diverse cellular processes and what are their contributions to carcinogenesis? Moreover, what is the contribution of all phorbol-ester effectors, which include PKCs and small G-protein regulators? We now face the challenge of dissecting the relative contribution of each DAG signal to cancer progression.
Topics: Apoptosis; Cell Cycle; Cell Proliferation; Diglycerides; Enzyme Activation; GTP Phosphohydrolases; Humans; Isoenzymes; Neoplasms; Neovascularization, Pathologic; Peptide Hydrolases; Phorbol Esters; Protein Kinase C
PubMed: 17384583
DOI: 10.1038/nrc2110 -
FASEB Journal : Official Publication of... Jun 2021Diacylglycerol kinases catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA). In humans, the alpha isoform (DGKα) has...
Diacylglycerol kinases catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA). In humans, the alpha isoform (DGKα) has emerged as a potential target in the treatment of cancer due to its anti-tumor and pro-immune responses. However, its mechanism of action at a molecular level is not fully understood. In this work, a systematic investigation of the role played by the membrane in the regulation of the enzymatic properties of human DGKα is presented. By using a cell-free system with purified DGKα and model membranes of variable physical and chemical properties, it is shown that membrane physical properties determine human DGKα substrate acyl chain specificity. In model membranes with a flat morphology; DGKα presents high enzymatic activity, but it is not able to differentiate DAG molecular species. Furthermore, DGKα enzymatic properties are insensitive to membrane intrinsic curvature. However, in the presence of model membranes with altered morphology, specifically the presence of physically curved membrane structures, DGKα bears substrate acyl chain specificity for palmitic acid-containing DAG. The present results identify changes in membrane morphology as one possible mechanism for the depletion of specific pools of DAG as well as the production of specific pools of PA by DGKα, adding an extra layer of regulation on the interconversion of these two potent lipid-signaling molecules. It is proposed that the interplay between membrane physical (shape) and chemical (lipid composition) properties guarantee a fine-tuned signal transduction system dependent on the levels and molecular species of DAG and PA.
Topics: Catalytic Domain; Cell Membrane; Diacylglycerol Kinase; Diglycerides; Humans; Phosphatidic Acids; Phosphorylation; Substrate Specificity
PubMed: 33977628
DOI: 10.1096/fj.202100264R -
Advances in Experimental Medicine and... 1992The content and molecular species composition of 1,2-diacylglycerol (DAG) in rat sciatic nerve was determined and compared with the molecular species profiles for... (Review)
Review
The content and molecular species composition of 1,2-diacylglycerol (DAG) in rat sciatic nerve was determined and compared with the molecular species profiles for glycerophospholipid classes in order to gain information concerning the metabolic pathways of DAG formation. The level of DAG in freshly dissected epineurium-free nerve (44 +/- 2 pmol/mg wet weight) was 10-40% of that in other tissues and cultured cells. The predominant DAG molecular species were 18:0/20:4 (30%) and 16:0/18:1 (17%). In comparison with phospholipid molecular species patterns, DAG was characterized by a substantial but lower proportion of the 18:0/20:4 species than was found in phosphoinositides, and a significant fraction of saturated species such as those found in phosphatidylcholine. In nerve from diabetic rats, both the content and arachidonoyl-containing molecular species of DAG were reduced. These species were also decreased in individual glycerophospholipids, except for phosphatidylinositol. The distribution of molecular species in phosphatidic acid (PA) did not resemble that of any other phospholipid. A large rise in DAG content occurred when nerve was incubated in vitro. Molecular species analysis indicated that phosphoinositides were the main source, especially during the initial period. This process was virtually abolished in a Ca(2+)-free medium and probably reflects a response to tissue injury. Evidence was obtained for the isomerization of DAG to 1,3-diacylglycerol during incubation. PA content and molecular species composition of incubated nerve did not change. However, inclusion of propranolol, a PA phosphatase inhibitor, caused a 40% accumulation of PA within 10 min, suggesting that formation of this phospholipid is continuous. These findings support the conclusion that DAG is principally derived from phosphoinositides by phospholipase C hydrolysis, but a minor fraction could be derived from phosphatidylcholine either by the action of phospholipase C or via phospholipase D and PA phosphatase. The metabolic origins of PA appear to be diverse.
Topics: Animals; Diabetes Mellitus, Experimental; Diglycerides; In Vitro Techniques; Peripheral Nerves; Phosphatidic Acids; Rats; Sciatic Nerve
PubMed: 1636507
DOI: 10.1007/978-1-4615-3426-6_37 -
BioFactors (Oxford, England) 2009Studies in animals and humans indicate that diets containing diacylglycerol (DAG) oil (containing >80% DAG) decrease body weight gain and body fat accumulation,... (Review)
Review
Studies in animals and humans indicate that diets containing diacylglycerol (DAG) oil (containing >80% DAG) decrease body weight gain and body fat accumulation, especially visceral fat. Body weight and body fat are controlled by energy expenditure, fat oxidation, fat storage capacity, and appetite control. Recent researches indicate that DAG oil, compared with conventional oils, has distinct metabolic effects. We review the evidence concerning the effects of DAG oil intake on fat oxidation and energy expenditure. In humans, dietary DAG is more susceptible to oxidation, and in animals 1,3-DAG, a major component of DAG oil, is rapidly oxidized. Short-term human studies with indirect calorimetry demonstrate greater fat oxidation with DAG oil consumption compared with triacylglycerol (TAG) oil consumption. Furthermore, DAG oil consumption for 14 days stimulates energy expenditure. Based on these reports, enhanced fat oxidation and energy expenditure by daily DAG oil intake could contribute to long-term reductions in body weight and fat accumulation. The literature provides support for the notion that dietary DAG is more rapidly oxidized than dietary TAG, and that, compared with TAG oil, DAG oil consumption increases whole body fat oxidation. The effects of DAG oil consumption on energy expenditure, however, remain inconclusive. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
Topics: Animals; Dietary Fats; Diglycerides; Energy Metabolism; Humans; Lipid Metabolism; Oils; Oxidation-Reduction
PubMed: 19449445
DOI: 10.1002/biof.25 -
STAR Protocols Jun 2021Small molecular probes designed for photopharmacology and opto-chemogenetics are rapidly gaining widespread recognition for investigations of transient receptor...
Small molecular probes designed for photopharmacology and opto-chemogenetics are rapidly gaining widespread recognition for investigations of transient receptor potential canonical (TRPC) channels. This protocol describes the use of three photoswitchable diacylglycerol analogs-PhoDAG-1, PhoDAG-3, and OptoDArG-for ultrarapid activation and deactivation of native TRPC2 channels in mouse vomeronasal sensory neurons and olfactory type B cells, as well as heterologously expressed human TRPC6 channels. Photoconversion can be achieved in mammalian tissue slices and enables all-optical stimulation and shutoff of TRPC channels. For complete details on the use and execution of this protocol, please refer to Leinders-Zufall et al. (2018).
Topics: Animals; Cells, Cultured; Cytological Techniques; Diglycerides; Mice; Olfactory Receptor Neurons; Photochemical Processes; Transient Receptor Potential Channels; Vomeronasal Organ
PubMed: 34027485
DOI: 10.1016/j.xpro.2021.100527 -
Methods in Molecular Biology (Clifton,... 1998
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Mutation Research Dec 1995A novel serine/threonine protein kinase regulated by phorbol esters and diacylglycerol (named PKD) has been identified. PKD contains a cysteine-rich repeat sequence... (Review)
Review
A novel serine/threonine protein kinase regulated by phorbol esters and diacylglycerol (named PKD) has been identified. PKD contains a cysteine-rich repeat sequence homologous to that seen in the regulatory domain of protein kinase C (PKC). A bacterially expressed NH2-terminal domain of PKD exhibited high affinity phorbol ester binding activity (Kd = 35 nM). Expression of PKD cDNA in COS cells conferred increased phorbol ester binding to intact cells. The catalytic domain of PKD contains all characteristic sequence motifs of serine protein kinases but shows only a low degree of sequence similarity to PKCs. The bacterially expressed catalytic domain of PKD efficiently phosphorylated the exogenous peptide substrate syntide-2 in serine but did not catalyse significant phosphorylation of a variety of other substrates utilised by PKCs and other major second messenger regulated kinases. PKD expressed in COS cells showed syntide-2 kinase activity that was stimulated by phorbol esters in the presence of phospholipids. We propose that PKD may be a novel component in the transduction of diacylglycerol and phorbol ester signals.
Topics: Amino Acid Sequence; Animals; Diglycerides; Humans; Molecular Sequence Data; Phorbol 12,13-Dibutyrate; Phorbol Esters; Protein Kinase C; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 8538623
DOI: 10.1016/0027-5107(95)00141-7 -
Diacylglycerol in Cationic Nanoparticles Stimulates Oxidative Stress-Mediated Death of Cancer Cells.Lipids Nov 2018Previous reports have suggested that cargo-free cationic nanoparticles (cNP) consisting of cationic monovalent lipids, such as 1,2-oleoyl-3-trimethylammonium-propane...
Previous reports have suggested that cargo-free cationic nanoparticles (cNP) consisting of cationic monovalent lipids, such as 1,2-oleoyl-3-trimethylammonium-propane (DOTAP), induce reactive oxygen species (ROS) generation and toxicity in cells. In addition, cNP containing six lysine residues (6K) and cargo (6K-cNP) exerted synergistic effects on ROS production and cell death in cancer cells. In this study, we investigated the effect of diacylglycerol (DAG) derived from egg phosphatidylcholine in nanoparticles (NP) on ROS-mediated cellular toxicity. When DAG was incorporated into cNP (D-cNP) or 6K-cNP (6K-D-cNP) up to 7.8 mol% at the expense of DOTAP, and treated with cells, ROS generation in cancer cells increased further in a DAG concentration-dependent manner compared with those of both cNP without DAG. Concomitantly, cancer cell viability was more decreased upon the treatment with DAG-containing cNP. Moreover, D-cNP or 6K-D-cNP exhibited enhanced uptake into cells under endocytosis-inhibited conditions. Taken together, these results suggested that the presence of DAG in NP stimulated the interaction of NP with cancer cells and the resulting ROS-mediated cytotoxicity.
Topics: Cell Line, Tumor; Cell Survival; Diglycerides; Humans; Nanoparticles; Oxidative Stress; Reactive Oxygen Species
PubMed: 30680740
DOI: 10.1002/lipd.12124