Disease relevance of diacylglycerol kinase inhibitor i

• The level of phosphatidic acid was increased by SPC only in the presence of AACOCF3, a specific inhibitor of phospholipase A2 (PLA2) and blocked by both pertussis toxin and R59022, an inhibitor of diacylglycerol kinase [1].
• Accumulation of inositol phosphates in NG108-15 neuroblastoma x glioma hybrid cells, pre-labeled for 24h to equilibrium, was stimulated by bradykinin, guanosine 5'-O-(3-thiotriphosphate) and the diacylglycerol kinase inhibitor R59022 [2].
• The present results show that the DAG kinase inhibitor, R 59022, suppressed tumor cell polarity and strongly inhibited cell locomotion at a concentration of 10(-4), thus supporting the earlier finding that an increased availability of DAGs can suppress the locomotor activity of Walker carcinosarcoma cells [3].

Psychiatry related information on diacylglycerol kinase inhibitor i

• R 59022, a compound which causes the accumulation of diacylglycerol by inhibition of the enzyme diacylglycerol kinase, was tested for its effect on stimulated motor activity of the longitudinal muscle from the guinea-pig ileum [4].

High impact information on diacylglycerol kinase inhibitor i

• Treatment of cells with two DAG kinase inhibitors, R59022 and R59949, blocked the IGF-I-dependent rise in nuclear DAG kinase activity and maintained elevated intranuclear levels of DAG [5].
• Membrane-permeant diacylglycerol analogues, which activated but did not down-regulate PKC, were devoid of growth-stimulating effects on melanocytes, even in the presence of the specific diacylglycerol kinase inhibitor, R59022 [6].
• In the present studies, we investigated in these cells protein phosphorylation stimulated by various protein kinase C activators, including 1-oleoyl-2-acetylglycerol in the presence of the diacylglycerol kinase inhibitor R59022, TPA, mezerein, and bryostatin [7].
• AtDGK7 activity was affected by pH, detergents, and the DGK inhibitor R59022 [8].
• Furthermore, re-translocation of PKCgamma was obviously hastened by co-expression with DGKgamma and was blocked by an inhibitor of DGK (R59022) [9].

Biological context of diacylglycerol kinase inhibitor i

• However, R59022, a DG kinase inhibitor, did not influence the accumulation of DG or PA, suggesting that platelet-derived growth factor stimulates mainly phospholipase D-catalyzed hydrolysis of phospholipids rather than phospholipase C-catalyzed hydrolysis in the second phase [10].
• It is concluded that in studies on the signal-transducing system coupled to inositol lipid metabolism R 59 022 might occupy a role comparable to cyclic AMP phosphodiesterase inhibitors, since it potentiates the effect of the putative second messenger diacylglycerol by preventing its rapid metabolism [11].
• Arabidopsis AtDGK7, the smallest member of plant diacylglycerol kinases (DGKs), displays unique biochemical features and saturates at low substrate concentration: the DGK inhibitor R59022 differentially affects AtDGK2 and AtDGK7 activity in vitro and alters plant growth and development [8].
• In spermatozoa stimulated with Ca2+/A23187 and the DAG kinase inhibitor R59022, a similar increase in DAG levels together with stimulation of acrosomal exocytosis were observed [12].
• The putative DGK inhibitor R59022 inhibited the 80-kDa DGK (IC50, 10 microM), but had little effect on the 150-kDa form [13].

Anatomical context of diacylglycerol kinase inhibitor i

• A diacylglycerol (DG) kinase inhibitor, R 59 022, potentiated superoxide anion (O2-) production in guinea pig polymorphonuclear leukocytes (PMNL) induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) [14].
• LPS stimulation only slightly increased intracellular levels of diacylglycerol, the natural activator of PKC, and pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did not affect LPS-stimulated TNF-alpha secretion [15].
• This inhibitory effect was not detected following R59022 treatment in portal vein [16].
• Increased protein synthesis response to insulin in fibroblasts treated with the diacylglycerol kinase inhibitor R59022 [17].
• A similar loss of InsP production upon stimulation of keratinocytes with 1.4 mM Ca2+ was seen after pretreatment with R59022, a DAG kinase inhibitor [18].

Associations of diacylglycerol kinase inhibitor i with other chemical compounds

• The diacylglycerol kinase inhibitors, dioctanoylethylene glycol and R59022 potentiated PLD stimulation by exogenous diacylglycerol but not by V(4+)-OOH [19].
• Phosphorylation of myosin light chains, formation of inositol phosphates and the mobilization of Ca2+ by thrombin are not affected by R59022 (10 microM) [20].
• Early DAG rises temporally overlapped respiratory burst initiation but PMN responses to hyphae were unchanged by a DAG kinase inhibitor, R59022, which blocks phosphorylation of DAG to PA and enhances DAG accumulation [21].
• The temporal relationship of the evolution of PA and DAG is further strengthened by experiments with ethanol and propranolol as inhibitors of the DAG/PA phosphohydrolase reaction and R59022 as an inhibitor of the DAG kinase reaction [22].
• The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells [23].

Gene context of diacylglycerol kinase inhibitor i

• In contrast, bFGF stimulated the phosphorylation of the Mr 80,000 (80K) cellular protein which is a major substrate of protein kinase C. This effect was potentiated by the diacylglycerol kinase inhibitor R59022 [24].
• The DGK inhibitor, R59022, inhibited DGK-II and to a lesser extent DGK-III, but little affected DGK-I activity [25].
• A diacylglycerol kinase inhibitor, R 59 022, potentiates superoxide anion production and 46-kDa protein phosphorylation in guinea pig polymorphonuclear leukocytes [14].
• R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet [11].
• R59022 (10 microM), which inhibits DG kinase and causes accumulation of endogenous DGs, inhibited the KCl-induced rise in [Ca2+]i to 2 +/- 0.2% of the control value; this inhibition was not affected by staurosporine [26].

Analytical, diagnostic and therapeutic context of diacylglycerol kinase inhibitor i

• To demonstrate that these effects were mediated by PKC activation, PKC isoforms were measured by Western blotting following R59022 exposure (50 mumol/l, 30 min) [27].

References