Disease relevance of D-1,2-Diacylglycerol

• Infection of astrocytes with Newcastle disease virus stimulated the production of 1,2-diacylglycerol, and resulted in the kinase-dependent expression of mRNAs encoding tumor necrosis factor (TNF), interferon alpha and beta, and interleukin 6 [1].
• Bradykinin also activated polyphosphoinositidase C in the dorsal root ganglion neurons, elevating levels of inositol(1,4,5)-trisphosphate and 1,2-diacylglycerol, an endogenous activator of PKC [2].
• 1,2-Diacylglycerol 3-glucosyltransferase synthesizes the major nonbilayer-prone lipid monoglucosyldiacylglycerol (MGlcDAG) in the membrane of Acholeplasma laidlawii, which is important for the spontaneous curvature, and is a regulatory site for the lipid surface charge density [3].
• Quantitative changes in the total mass and the molecular species of 1,2-diacyl-sn-glycerol (DAG) and phosphatidic acid (PA) formed upon muscarinic receptor activation were studied in cultured human SK-N-SH neuroblastoma cells [4].
• Emerging evidence suggests that active relaxation, expressed as augmented content or activity of effectors within the cyclic AMP signaling pathway and suppressed content or activity of effectors in the inositol 1,4,5-trisphosphate/1,2-diacylglycerol signaling pathway, may be occurring in VSMCs of the splanchnic circulation in portal hypertension [5].

High impact information on D-1,2-Diacylglycerol

• SMase activation is secondary to the generation of 1,2-diacylglycerol (DAG) produced by a TNF-responsive PC-specific phospholipase C (PC-PLC) [6].
• These findings suggest that a source other than phosphoinositides exists for the generation of 1,2-diacylglycerol and that the Ha-ras oncogene specifically activates this novel pathway for 1,2-diacylglycerol production [7].
• The bifurcating nature of the signalling system is exemplified by the fact that the other product of PtdIns(4,5)P2 hydrolysis, 1,2-diacylglycerol, can alter cellular function by activating protein kinase C, the cellular target for several tumour-promoting agents such as the phorbol esters [8].
• However, either one in combination with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), which is structurally related to 1,2-diacylglycerol, induces in lymphoid cell populations the expression of receptors for interleukin-2 (IL-2), the secretion of IL-2 and cell proliferation as measured by 3H-thymidine uptake [9].
• The role of cyclic AMP may involve either inhibition of Ca2+ mobilization to the cytosol or stimulation of intracellular Ca2+ uptake, and in addition inhibition of 1,2-diacylglycerol formation [10].

Chemical compound and disease context of D-1,2-Diacylglycerol

• Vasoactive intestinal contractor (VIC) caused a series of biochemical events, including the temporal biphasic accumulation of 1,2-diacylglycerol (DAG), transient formation of Ins(1,4,5)P3, and increase in intracellular free Ca2+ [( Ca2+]i) in neuroblastoma NG108-15 cells [11].
• The content and composition of 1,2-diacyl-sn-glycerol (1,2-DAG) was determined in hepatocytes from saline (0.9% NaCl)- and Escherichia coli endotoxin (ET)-infused rats upon continuous vasopressin (VP) (10(-8) M) stimulation [12].
• Clostridium perfringens alpha-toxin induces the generation of superoxide anion (O2(-)) via production of 1,2-diacylglycerol (DG) in rabbit neutrophils [13].
• These data are consistent with the possibility that the elevation in lesional 1,2-diacylglycerol content may account, in part, for the previously reported reduction of protein kinase C activity in psoriasis (Horn, Marks, Fisher, et al: J Invest Dermatol 88:220-222, 1987) [14].
• Impact of alpha-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol [15].

Biological context of D-1,2-Diacylglycerol

• Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene [7].
• Thyroid-stimulating hormone and insulin-like growth factor-1 synergize to elevate 1,2-diacylglycerol in rat thyroid cells. Stimulation of DNA synthesis via interaction between lipid and adenylyl cyclase signal transduction systems [16].
• Physiological and electrophysiological techniques were employed to investigate the possibility that a second-messenger lipid, 1,2-diacylglycerol, is involved in the transduction of opening stimuli [17].
• Identification of the parasite transferrin receptor of Plasmodium falciparum-infected erythrocytes and its acylation via 1,2-diacyl-sn-glycerol [18].
• Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in vitro translation or COS-1 cell transfection stimulated the Ras exchange activity of Vav in the absence of detectable tyrosine phosphorylation [19].

Anatomical context of D-1,2-Diacylglycerol

• Accumulation of 1,2-diacylglycerol in the plasma membrane may lead to echinocyte transformation of erythrocytes [20].
• Recent evidence has suggested that pancreatic islets isolated from rats synthesize 1,2-diacyl-sn-glycerol (DAG) de novo from glucose and that this process may constitute the long-sought link between the metabolism of glucose and the induction of insulin secretion [21].
• METHODS: In adult and kitten antrum isolated smooth muscle cell contraction, levels of 1,2-diacylglycerol (DAG) and IP3 were assessed in response to cholecystokinin (CCK) [22].
• In the present work, contamination of thylakoids by envelope membranes was determined by measuring the 1,2-diacylglycerol 3-beta-galactosyltransferase [monogalactosyldiacylglycerol (MGDG) synthase; UDPgalactose: 1,2-diacylglycerol 3-beta-D-galactosyltransferase, EC 2.4.1.46] in the different chloroplast subfractions [23].
• Leukocyte chemoattraction by 1,2-diacylglycerol [24].

Associations of D-1,2-Diacylglycerol with other chemical compounds

• Because phorbol myristate acetate stimulates DNA synthesis, the effects of TSH, IGF-1 and insulin on FRTL-5 cell content of 1,2-diacylglycerol (1,2-DG), the endogenous activator of protein kinase C, were measured [16].
• Stimulation of platelet G protein-coupled receptors results in the cleavage of phosphatidylinositol 4,5-trisphosphate (PIP(2)) into inositol 1,4,5-trisphosphate and 1,2-diacylglycerol by phospholipase C (PLCbeta) [25].
• Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphatidylinositol-specific phospholipase C (PI-PLC) generates two second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol [26].
• It was suggested that the phosphocholine arises from constitutive hydrolysis of phosphatidylcholine by phospholipase C, an activity that would also account for the elevated 1,2-diacylglycerol found in ras-transformed cells [27].
• Phosphatidylcholine is a quantitatively more important source of increased 1,2-diacylglycerol than is phosphatidylinositol in mast cells [28].

Gene context of D-1,2-Diacylglycerol

• The CD28 molecule also appears to activate polyphosphoinositide (InsPL)-specific phospholipase C (PLC) activity in Jurkat cells, as demonstrated by PtdInsP2 breakdown, InsP3 and 1,2-diacylglycerol generation and PtdIns resynthesis [29].
• In response to the activation of phospholipase C by toxic drugs and the local production of 1,2-diacylglycerol, PKC is translocated to the cell membrane where it phosphorylates P-gp [30].
• The present studies aim to investigate the mechanism of TGF beta 1 signaling and to explore whether TGF beta 1's pathway involves activation of PKC by 1,2-Diacylglycerol (DAG) and/or stimulation of a CAPK by ceramide [31].
• However, the mechanism of SRIF's action on TRH is not clear, since SRIF did not affect the intracellular responses by TRH, neither intracellular Ca2+ mobilization nor the increase of 1,2-diacylglycerol formation following the breakdown of polyphosphoinositides [32].
• The hDGKzeta displays stereoselectivity for 1,2-diacylglycerol species in comparison to 1,3-diacylglycerol, but does not exhibit any specificity for molecular species of long chain diacylglycerols [33].

Analytical, diagnostic and therapeutic context of D-1,2-Diacylglycerol

• Microinjection of p21Ha-ras proteins into Xenopus laevis oocytes induces a rapid increase of 1,2-diacylglycerol (DAG) levels [34].
• For this purpose, platelets were prelabeled with [2-3H]glycerol and the loss of radioactivity from the saturated, monoenoic, dienoic, trienoic, tetraenoic, and greater than tetraenoic [3H]phosphatidylinositols was determined after conversion to their 1,2-diacylglycerol acetate derivatives and fractionation by argentation thin layer chromatography [35].
• The molecular species of 1,2-diacylglycerol in control and agonist-stimulated rat hepatocytes were analyzed by high performance liquid chromatography [36].
• In contrast, no increases in 1,2-diacylglycerol concentration were observed in plantaris muscles at shorter intervals than 15 days after denervation [37].
• 1,2-Diacylglycerol (DAG) was measured in neutral lipid extracts from isolated hepatocytes using high pressure liquid chromatography followed by refractive index detection [38].

References