Disease relevance of Glycerylphosphoinositol

• Acetylcholine stimulates selective liberation and re-esterification of arachidonate and accumulation of inositol phosphates and glycerophosphoinositol in C62B glioma cells [1].
• In intact cells, cholera toxin and pertussis toxin stimulated phospholipase A2 to enhance metabolism of phosphatidylinositol to lysophosphatidylinositol and glycerophosphoinositol, with time courses similar to their stimulation of PGE2 synthesis [2].
• Data from the evaluation of thioalkyl and amidoalkyl glycerophosphocholine and of glycerophosphoinositol EL analogs against different experimental tumors in vitro (HL60 and K562 human leukemia cells, BG1 and BG3 ovarian adenocarcinomas) are presented [3].

High impact information on Glycerylphosphoinositol

• Expression of wild-type MIR16 (renamed GDE1), but not two catalytic domain mutants (E97A/D99A and H112A), leads to a dramatic increase in glycerophosphoinositol phosphodiesterase (GPI-PDE) activity in HEK 293T cells [4].
• GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors [4].
• Furthermore, glycerophospho[3H]choline accumulation requires the transporter encoded by GIT1, a known glycerophosphoinositol transporter [5].
• Reorganization of actin cytoskeleton by the phosphoinositide metabolite glycerophosphoinositol 4-phosphate [6].
• Overexpression of unrelated phosphate transporters or a glycerophosphoinositol transporter in the pho84Delta strain suppresses the PHO5 constitutive phenotype [7].

Biological context of Glycerylphosphoinositol

• In particular, our data do not support the reported correlation between elevated glycerophosphoinositol (GroPIns) levels and transformation of cells by membrane and cytoplasmic oncogenes which has been reported by other workers [8].
• Another mutant was complemented by a single open reading frame (ORF) termed GIT1 (glycerophosphoinositol) [9].
• In glycerophosphoinositol (PI) species, it appears that an RCO- ion is formed during negative ion MS/MS, possibly to steric interference from the bulky phosphoinositol headgroup that prevents cyclization (and subsequent stabilization) of the ion described for PE species [10].
• ET-3-induced hydrolysis of phosphoinositides was characterized by the production of various inositol phosphates and of glycerophosphoinositol [11].
• Here we have analyzed the glycerophosphoinositol levels in cells that are considered models of cell differentiation [12].

Anatomical context of Glycerylphosphoinositol

• 1. Lysosomes from rat liver contain two enzymic systems for hydrolysing phosphatidyl-inositol: a deacylation via lysophosphatidylinositol producing glycerophosphoinositol and non-esterified fatty acid, and a phospholipase C-like cleavage into inositol 1-phosphate and diaclygycerol [13].
• Treatment of ewes with PAF in vivo reduced inositol monophosphate (IP1) generated by oxytocin (10(-6) M) by 56.4%, compared to that in endometrium from vehicle-treated controls, and also inhibited the incorporation of 3H-inositol into glycerophosphoinositol (GPI) [14].
• Analysis of the individual metabolites of inositol phospholipid metabolism formed in response to noradrenaline in PKC-depleted astrocytes revealed potentiated accumulations of radiolabelled glycerophosphoinositol (GPI), inositol monophosphate (IP1) and inositol bisphosphate (IP2) but not inositol trisphosphate (IP3) when compared to controls [15].
• We here show that, in an in vitro model of the BBB based on a co-culture of endothelial cells (EC) and glia, the natural compound glycerophosphoinositol (GPI) may replicate the effects of DEX [16].
• In a different neuronal cell line, PC12 cells, increased glycerophosphoinositol levels characterized the differentiated cells [12].

Associations of Glycerylphosphoinositol with other chemical compounds

• Git1p appears to act as a H(+)-symporter, and neither inositol nor phosphate effectively compete with glycerophosphoinositol for transport by Git1p [17].
• At 5 weeks of age, exposure to a maximal concentration of noradrenaline brought about a significant increase in lipid radioactivity in WKY and in glycerophosphoinositol and glycerophosphoinositol 4-phosphate in SHR [18].
• Glycerophosphoinositol and dexamethasone improve transendothelial electrical resistance in an in vitro study of the blood-brain barrier [16].
• Histamine stimulation of cultured human umbilical vein endothelial cells induced dose- and time-dependent increases in glycerophosphoinositol (GroPIns), inositol-1-phosphate (InsP), inositolbisphosphate (InsP2) and inositoltrisphosphate (InsP3) in addition to release of thromboxane A2 and prostacyclin [19].
• Posttranscriptional regulation of Git1p, the glycerophosphoinositol/glycerophosphocholine transporter of Saccharomyces cerevisiae [20].

Gene context of Glycerylphosphoinositol

• Based on these observations we suggest that high glycerophosphoinositol levels characterize cellular phenomena associated with the activation of ras/mitogen-activated protein kinase pathways [12].
• A genetic screen identified Pho86p, which is required for targeting of the major phosphate transporter (Pho84p) to the plasma membrane, as affecting the utilization of phosphatidylinositol and glycerophosphoinositol [21].
• The naturally occurring phosphoinositide metabolite, glycerophosphoinositol 4-phosphate, has recently been shown to induce rearrangements in the actin cytoskeleton through modulation of the small GTPases, Rac and Rho [22].
• Transformation of rodent fibroblasts by cytoplasmic (mos, raf) and membrane-associated (ras, src, met, trk), but not nuclear (myc, fos) oncogenes results specifically in a very significant elevation of intracellular levels of glycerophosphoinositol (GPI) [23].
• Furthermore, ET-induced accumulation of the phospholipase A2/phospholipase B-derived inositol phospholipid metabolite, glycerophosphoinositol, was not different between control and phorbol-treated hVMSC [24].

Analytical, diagnostic and therapeutic context of Glycerylphosphoinositol

• In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2 [25].
• HPLC identification of the phosphoinositide metabolites of the adrenal cells showed that they include glycerophosphoinositol and glycerophosphoinositol phosphate (which would arise by sequential action of phospholipase A1 or A2 and lysophospholipase) [26].

References