Disease relevance of Diradylglycerol

• We hypothesized that fatty liver might be associated with the accumulation of 1,2-sn-diradylglycerol and subsequent activation of protein kinase C. Several lines of evidence indicate that cancers might develop secondary to abnormalities in protein kinase C-mediated signal transduction [1].
• 1,2(2,3)-Diradylglycero O-(p-nitrophenyl) n-hexylphosphonates were synthesized, with the diradylglycerol moiety being di-O-octylglycerol, 1-O-hexadecyl-2-O-pyrenedecanylglycerol, or 1-O-octyl-2-oleoyl-glycerol, and tested for their ability to inactivate lipases from Chromobacterium viscosum (CVL) and Rhizopus oryzae (ROL) [2].

High impact information on Diradylglycerol

• Thus, these data suggest a second messenger role for phosphatidic acid-derived diradylglycerol in the induction of TNF-alpha gene expression [3].
• The generation of diradylglycerol (DRG) and phosphatidic acid (PdtOH) was investigated in neutrophils primed with granulocyte-macrophage colony-stimulating factor (GM-CSF) [4].
• Lisofylline does not inhibit lipopolysaccharide-induced activation of phosphatidylinositol-specific phospholipase C and generation of phosphatidylinositol-derived diradylglycerol [5].
• In vitro assessment of hCPT1 and hCEPT1 derived cholinephosphotransferase activities also revealed differences in diradylglycerol specificities including their capacity to synthesize platelet-activating factor and platelet-activating factor precursor [6].
• In addition, interleukin-2 failed to stimulate de novo synthesis of diradylglycerol [7].

Biological context of Diradylglycerol

• Effects on the latter species, as well as a lack of effect on fMLP-stimulated inositol phosphate release, implied that cAMP affected diradylglycerol generation from a source other than phospholipase C-dependent phosphoinositide hydrolysis, since phosphatidylinositols do not contain appreciable quantities of the 1-O-alkyl linkage [8].
• Diradylglycerol synergizes with an anionic amphiphile to activate superoxide generation and phosphorylation of p47phox in a cell-free system from human neutrophils [9].
• Role of phospholipase D-derived diradylglycerol in the activation of the human neutrophil respiratory burst oxidase. Inhibition by phosphatidic acid phosphohydrolase inhibitors [10].
• Formation of second messenger diradylglycerol in murine peritoneal macrophages is altered after in vivo (n-3) polyunsaturated fatty acid supplementation [11].
• Fluoride induces a very large increase in diradylglycerol mass (both 1,2-diacylglycerol (DAG) and 1-O-alkyl,2-acylglycerol (EAG)), with kinetics similar to superoxide generation [12].

Anatomical context of Diradylglycerol

• Dynamics of the diradylglycerol responses of stimulated phagocytes [13].
• Diradylglycerol increased 2- to 3-fold in both whole cells and plasma membranes after stimulation, but was only a minor component compared with TAG [14].
• Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices [15].
• 1. After the degradation of cell-surface sphingomyelin (SM) by exogenous sphingomyelinase (SMase), the resynthesis of SM by baby-hamster kidney (BHK) and human leukaemia-60 (HL-60) cells was examined in relation to utilization of substrate phosphatidylcholine (PtdCho) and generation of the expected product, diradylglycerol (DRG) [16].
• It is therefore concluded that most of the GP-2 secreted by the pancreas of anaesthetized rats under resting conditions is released from the membrane by a phospholipase C which hydrolyses the phosphodiester bond linking GP-2 to its diradylglycerol anchor [17].

Associations of Diradylglycerol with other chemical compounds

• Both C2 ceramides and sphingoid bases partially inhibited the diradylglycerol formation by the phosphatidylcholine-specific phospholipase D pathway [18].
• Human neutrophils treated with phorbol 12-myristate 13-acetate (PMA) or dioctanoylglycerol exhibited a large (10-fold), sustained accumulation of the mass of diradylglycerol, beginning 1 min after stimulation and continuing for 30 to 60 min [19].
• Cyclic AMP-elevating agents block chemoattractant activation of diradylglycerol generation by inhibiting phospholipase D activation [8].
• When radiolabeled CTLL-2 cells were challenged with interleukin-2, no change in the cellular content of phosphatidylcholine nor phosphatidylethanolamine was observed thereby ruling out phospholipase C activity as the source of diradylglycerol [7].
• GPC was initially isolated by thin-layer chromatography (TLC), the phosphocholine group was hydrolyzed, and the resultant diradylglycerol was derivatized with 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin (CMMC) [20].

Gene context of Diradylglycerol

• We used an expression system devoid of endogenous cholinephosphotransferase and ethanolaminephosphotransferase activities to assess the diradylglycerol specificity of CEPT1 [21].
• This PKC, in turn phosphorylates a plasma membrane component resulting in PLD activation and a second outpouring of diradylglycerol [22].
• Phospholipase D-mediated diradylglycerol formation coincides with H2O2 and lactoferrin release in adherent human neutrophils [23].
• Purified amphiphilic AChE was treated with PI-specific phospholipase C in order to release the diradylglycerol moiety from the membrane anchoring domain [24].
• The occurrence and regulation of 1-ether-linked diradylglycerol in human neutrophils were investigated using a sensitive and practical analytical mass method which distinguishes 1-O-alkyl- (EAG) versus 1-acyl (DAG) diglycerides [25].

Analytical, diagnostic and therapeutic context of Diradylglycerol

• In addition, the derivatized diradylglycerol species were unequivocably identified by continuous flow fast-atom bombardment mass spectrometry [20].
• A method for ceramide (CER) and diradylglycerol (DG) determination after normal-phase HPLC separation was developed [26].

References