Disease relevance of Oleoylacetylglycerol

• The possibility that this phosphorylation was related to activation of Ca2+ phospholipid-dependent protein kinase was suggested by the fact that phospholipid breakdown induced by exogenous treatment of the cells with Clostridium perfringens phospholipase C and 1-oleoyl-2-acetylglycerol also enhanced Mr 54,000 cellular protein phosphorylation [1].
• The melanogenic responses to 1-oleoyl-2-acetylglycerol and ultraviolet radiation were unaffected by inhibition of protein kinase C with Ro31-8220, or ablation by downregulation with 500 nM TPA, in human melanocytes and melanoma cells [2].
• We found that treatment of KM12L4a human colon cancer cells with the diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (OAG) significantly reduced [14C]ADR and [3H]VCR accumulation in the cells [3].
• In contrast, 1-oleoyl-2-acetylglycerol induced rapid actin reorganization and shape change, presumably bypassing the pertussis blockade [4].
• This study shows that the membrane-permeable stereospecific 1-oleoyl-2-acetyl-sn-glycerol (OAG), which is the analog of the natural 1,2-diacylglycerol (DAG), can stimulate the growth of ascites tumor cells [5].

High impact information on Oleoylacetylglycerol

• TPA and 1-oleoyl-2-acetylglycerol also rapidly repress K1 and K10 mRNA expression when added to differentiating keratinocyte cultures already expressing these markers [6].
• Whole-cell patch clamping of guard-cell protoplasts of Vicia faba revealed that 1,2-dihexanoylglycerol and 1-oleoyl-2-acetylglycerol activated an ATP-dependent, voltage-independent current, suggesting activation of an electrogenic ion pump such as the H+ pump [7].
• However, a protein kinase C activator (phorbol 12-myristate 13-acetate) and synthetic diacylglycerol analogs (1-oleoyl-2-acetyl-sn-glycerol and dioctanoglycerol) caused marked neurite retraction [8].
• The synthetic diacylglycerols 1,2-dioctanoylglycerol (diC8) and 1-oleoyl-2-acetylglycerol strongly enhanced IFN-beta 2, but not IFN-beta 1, gene expression in human fibroblasts (FS-4 strain) [9].
• Several activators of protein kinase C (1-oleoyl-2-acetylglycerol, phorbol 12,13-diacetate, and phorbol 12,13-dibutyrate) were tested for their ability to modulate AcChoR function in embryonic chicken sympathetic ganglion neurons [10].

Chemical compound and disease context of Oleoylacetylglycerol

• In ascites tumor cells, phosphoinositide metabolism can be activated by short-term treatment with exogenously added 1-oleoyl-2-acetyl-sn-glycerol (OAG), which is the membrane-permeable analog of diacylglycerides (DAG) [11].
• Guanine nucleotides activate cytosolic phospholipase C of ascites tumour cells stimulated by 1-oleoyl-2-acetyl-sn-glycerol [12].

Biological context of Oleoylacetylglycerol

• In addition, S6 phosphorylation was increased in serum-starved CEF incubated with the diacylglycerol derivative, 1-oleoyl-2-acetylglycerol [13].
• Thus, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate and mezerein potently inhibit cellular proliferation (by greater than 90%), whereas the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol markedly stimulates proliferation of serum-starved, quiescent M5076 cells [14].
• The concentration needed for half-maximal inhibition (IC50) was 2.8 +/- 1.5 X 10(-6) M for the kinase acting on endogenous diacylglycerol and 3.3 +/- 0.4 X 10(-6) M when 1-oleoyl-2-acetylglycerol (OAG) was added exogenously as substrate [15].
• Activation of PKC by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol also resulted in down-regulation of PAF-R mRNA accumulation, whereas the inactive phorbol diester 4alpha-PMA was ineffective [16].
• In addition, incubation of U937 cells with C(6)-ceramide and/or H7 (a selective PKC inhibitor) reduced U937 cell viability; whereas pretreatment of the cells with a PKC activator, PMA or 1-oleoyl-2-acetylglycerol (OAG), attenuated D609-induced U937 cell apoptosis [17].

Anatomical context of Oleoylacetylglycerol

• We report here that addition of the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG) to quiescent cultures of Swiss 3T3 cells caused a marked increase in the rate of ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na+/K+ pump [18].
• As judged by indirect immunofluorescence, phorbol 12,13-dibutyrate and 1-oleoyl-2-acetylglycerol induced a rapid, concentration-dependent decrease of about 50% in the surface expression of the T3 antigen on human T lymphoblasts, and of T3 and the T-cell antigen receptor on HPB-ALL cells [19].
• The treatment of HL-60 and U-937 cell lines with 1-oleoyl-2-acetylglycerol, a synthetic analog of diacylglycerol that, like TPA, stimulates protein kinase C activity, was followed by early and transient induction of c-fos mRNA in the absence of terminal macrophage differentiation [20].
• The addition of 1-oleoyl-2-acetylglycerol (OAG), or phorbol-12-myristate-13-acetate (PMA) to platelets induced the phosphorylation of a 47,000 dalton protein (47 Kd), fusion of granule membranes with membranes of the surface connected canalicular system, the formation of large vesicles and the secretion of serotonin [21].
• We compared the effect of pretreating intact monoblastoid U937 cells with TPA or the diacylglycerol derivative, 1-oleoyl-2-acetylglycerol (OAG), by studying the protein kinase C dependent and independent histone phosphotransferase activity, the phosphorylation of endogenous substrates, and the ability to stimulate differentiation [22].

Associations of Oleoylacetylglycerol with other chemical compounds

• Phorbol esters and 1-oleyl, 2-acetylglycerol acted in synergy with ionomycin to liberate membrane Ca as detected by decreased fluorescence of chlortetracycline in prelabeled cells [23].
• To elucidate possible functions of elevation of endogenous diacylglycerol induced by thyrotropin-releasing hormone in pituitary cells, we have studied the actions of two synthetic diacylglycerols, sn-1-oleoyl-2-acetylglycerol (OAG) and sn-1,2-dioctanoylglycerol (DiC8), on cytosolic free calcium concentration ([Ca2+]i) in GH4C1 cells [24].
• Phorbol ester and 1-oleoyl-2-acetylglycerol inhibit angiotensin activation of phospholipase C in cultured vascular smooth muscle cells [25].
• Further, the PKC inhibitor, 1-O-hexadecyl-2-O-methylglycerol blocked tyrosine phosphorylation induced by 1-oleoyl-2-acetylglycerol [26].
• Pretreatment of hepatocytes with phorbol ester (PMA) or 1-oleoyl-2-acetylglycerol totally inhibited the effects of phenylephrine in elevating the cytosolic free Ca2+; half-maximal inhibitory effects occurred at PMA and 1-oleoyl-2-acetylglycerol concentrations of 1 ng/ml and 12 micrograms/ml, respectively [27].

Gene context of Oleoylacetylglycerol

• Previously, we have shown that 1-oleoyl-2-acetylglycerol (OAG) functions as an agonist for human polymorphonuclear leukocytes (PMNL) in stimulating 5-LO product formation [28].
• The activation of PKC with PMA or 1-oleoyl-2-acetyl-sn-glycerol could mimic the TCR signal by inducing the expression of Fas but not FasL [29].
• The diacylglycerol analog oleoylacetylglycerol also reduced ABCA1 protein levels and increased its serine phosphorylation, suggesting that PLD2-generated diacylglycerols promote the destabilizing phosphorylation of ABCA1 [30].
• Although the activating effect of PIP(3) on TRPC6 is reminiscent to that of 1-oleoyl-2-acetyl-sn-glycerol, this activation is not attributable to the diacylglycerol substructure of PIP(3) since other phosphoinositides failed to trigger Ca(2+) responses [31].
• RAW264.7 cells treated with DAG analogue 1-oleoyl-2-acetyl-sn-glycerol, in the presence of interferon-gamma, produced TNF-alpha [32].

Analytical, diagnostic and therapeutic context of Oleoylacetylglycerol

• In whole-cell recordings, extracellularly applied 1-oleoyl-2-acetylglycerol (OAG; 0.5-5 microM) mimicked the degree of block and occluded the block of sustained current by BK [33].
• However, the activity of these channels is strongly depressed after treatment with diacylglycerols (1-oleyl 2-acetylglycerol and 1,2-dioctanoylglycerol) [34].
• Treatment of co-cultures with exogenous phospholipase C or 1-oleoyl-2-acetylglycerol (OAG) resulted in communication inhibition, suggesting that protein kinase C activation is involved in the mechanism of phorbol ester-mediated communication inhibition [35].
• These results suggest that the release of mGRH-IR from placental cells is mediated, at least in part, by the activation of protein kinase C. The HPLC elution profiles of mGRH-IR released from placental cells under basal and 1-oleoyl-2-acetyl-sn-glycerol-stimulated conditions were similar to those in placental tissue [36].
• Inhibition of phorbol ester stimulated superoxide production by 1-oleoyl-2-acetyl-sn-glycerol (OAG); fact or artefact [37]?

References