Phosphatidylinositol-Specific Phospholipase C can inhibit the proliferation of and suppress the phagocytosis of Müller cells via modulating PI3K/AKT signaling pathway
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE212054 | GEO | 2022/09/01
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC2947483 | biostudies-literature
Project description:Gliomas are primary brain tumors with poor prognosis that exhibit frequent abnormalities in phosphatidylinositol 3-kinase (PI3 kinase) signaling. We investigated the molecular mechanism of action of the isoform-selective class I PI3 kinase and mTOR inhibitor PI-103 in human glioma cells. The potent inhibitory effects of PI-103 on the PI3 kinase pathway were quantified. PI-103 and the mTOR inhibitor rapamycin both inhibited ribosomal protein S6 phosphorylation but there were clear differences in the response of upstream components of the PI3 kinase pathway, such as phosphorylation of Thr308-AKT, that were inhibited by PI-103 but not rapamycin. Gene expression profiling identified altered expression of genes encoding regulators of the cell cycle and cholesterol metabolism, and genes modulated by insulin or IGF1 signaling, rapamycin treatment or nutrient starvation. PI-103 decreased expression of positive regulators of G1/S phase progression and increased expression of the negative cell cycle regulator p27kip1. A reversible PI-103-mediated G1 cell cycle arrest occurred without significant apoptosis, consistent with the altered gene expression detected. PI-103 induced vacuolation and processing of LC-3i to LC-3ii, which are features of an autophagic response. In contrast to PI-103, LY294002 and PI-387 induced apoptosis, indicative of likely off-target effects. PI-103 interacted synergistically or additively with cytotoxic agents used in the treatment of glioma, namely vincristine, BCNU and temozolomide. Compared to individual treatments, the combination of PI-103 with temozolomide significantly improved the response of U87MG human glioma xenografts. Our results support the therapeutic potential for PI3 kinase inhibitors with a PI-103-like profile as therapeutic agents for the treatment of glioma. Keywords: Key words: PI-103, glioma, PI3 kinase, mTOR, cell cycle, cytostasis
2009-04-21 | GSE12175 | GEO
Project description:au13-01_pi-plc What are the genes that are regulated by basal PI-PLC? Arabidopsis thaliana cells in suspension (5-days old). Cultivated in environment (middle) Gamborg+2,4-D. Added inhibitors 4 hr before extraction of the RNAs. We try to determine the role of phospholipases C ( PI-PLC) in the control of the basal expression of the genes of suspension of Arabidopsis thaliana. A first experience in which we used the edelfosine as inhibitor allowed us to identify numerous genes the basal expression of which is altered by this inhibition. We want to confirm these results with another inhibitor.
2013-09-01 | GSE46941 | GEO
Project description:The regulation of phospholipid biosynthesis in Saccharomyces cerevisiae through cis-acting upstream activating sequence inositol (UASino) and trans-acting elements, such as the INO2-INO4 complex and OPI1 by inositol supplementation in growth is thoroughly studied. In this study, we provide evidence for the regulation of lipid biosynthesis by phosphatidylinositol-specific phospholipase C (PLC) through UASino and two trans-acting elements. Gene expression analysis and radiolabelling experiments demonstrated that the overexpression of rice PLC in yeast cells altered phospholipid biosynthesis at the levels of transcriptional and enzyme activity.
2012-09-01 | GSE35745 | GEO
Project description:The regulation of phospholipid biosynthesis in Saccharomyces cerevisiae through cis-acting upstream activating sequence inositol (UASino) and trans-acting elements, such as the INO2-INO4 complex and OPI1 by inositol supplementation in growth is thoroughly studied. In this study, we provide evidence for the regulation of lipid biosynthesis by phosphatidylinositol-specific phospholipase C (PLC) through UASino and two trans-acting elements. Gene expression analysis and radiolabelling experiments demonstrated that the overexpression of rice PLC in yeast cells altered phospholipid biosynthesis at the levels of transcriptional and enzyme activity.
2012-04-24 | GSE35677 | GEO
Project description: Not available
| S-EPMC2417189 | biostudies-literature
Project description:A proteomics strategy was used to identify putative GPI-APs from adult B. malayi. Three different sample types were prepared for analysis. Firstly, intact adult worms were treated with PI-PLC to enzymatically release and solubilize the protein away from the lipid moiety. A mock-treatment with no PI-PLC was performed as a negative control. The samples derived from treatment of the intact worms have been named “Surface” but it should be noted that the proteins could originate from any exposed surface like the mouth, vagina, or rectum of the worm. Secondly, a membrane fraction of B. malayi adult female worms was prepared by ultracentrifugation of a total lysate in a sucrose buffer to separate membrane proteins from soluble proteins. This membrane fraction was also treated with PI-PLC or mock-treated without PI-PLC as a negative control. Lastly, a GPI-AP enriched sample was prepared by performing a series of organic solvent partitions to extract GPI-APs from a membrane fraction. This sample was not treated with PI-PLC. Proteins in all three samples types were digested with trypsin and the resulting peptides analyzed by LC-MS/MS.
2019-11-12 | PXD014949 | Pride
Project description:we used hydrogen deuterium exchange masss spec (HDX-MS) to define the exchange kinetics of PLC-y1 as it interacts with the kinase domain of FGFR1, and liposomes containing PIP2, in order to understand how PLC-y isozymes operate at membranes. We show that the binding of FGFR1k to PLC-y1 increases deuterium incorporation within the interface between the regulatory domains and the catalytic core. Importantly, the addition of liposomes further increase deuterium exchange within the same region.
2022-06-14 | PXD030492 | Pride
Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.
2013-05-01 | E-GEOD-42762 | biostudies-arrayexpress
Project description:au13-01_pi-plc What are the genes that are regulated by basal PI-PLC? Arabidopsis thaliana cells in suspension (5-days old). Cultivated in environment (middle) Gamborg+2,4-D. Added inhibitors 4 hr before extraction of the RNAs. We try to determine the role of phospholipases C ( PI-PLC) in the control of the basal expression of the genes of suspension of Arabidopsis thaliana. A first experience in which we used the edelfosine as inhibitor allowed us to identify numerous genes the basal expression of which is altered by this inhibition. We want to confirm these results with another inhibitor. 4 dye-swap - treated vs untreated comparison - treatment variations
2013-09-01 | E-GEOD-46941 | biostudies-arrayexpress