Phosphatidylcholine in brain

Jackson, S.N. Wang, H-Y.J. Woods, A.S. In situ structural characterization of phosphatidylcholines in brain tissue using MALDI-MS/MS. J. Am. Soc. Mass Spectrom. 2005,16, 2052-2056. 

Koizumi S, Yamamoto S, Hayasaka T, Konishi Y, Yamaguchi-Okada M, Goto-Inoue N, Sugiura Y, Setou M, Namba H (2010) Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain. Neuroscience 168 219-225. doi 10.1016/j.neuroscience.2010.03.056... 

Mikawa S, Suzuki M, Fujimoto C, Sato K (2009) Imaging of phosphatidylcholines in the adult rat brain using MALDI-TOF MS. Neurosci Lett 451 45—49. doi 10.1016/j.neulet.2008.12.035... 

The closely related derivative, phosphatidylcholine, occurs in most plant and animal cells and is the most abundant lipid in mammalian cells. Another type of lipid is represented by sphingomyelin, which is found in high concentration in brain tissue, other nervous tissue, and erythrocytes. 

Phosphatidylcholines, above all lecithin, occur in millimolar concentrations in serum and bile. Acetylcholine (ACh) occurs in brain and nerve extracts together with its degradation product, choline. 

H-leucine-labeled protein and 14C-choline-labeled phosphatidylcholine in discrete regions of the rat brain Loh, Horace H. Hitzeman, Robert J. 

Ferris et al., 1982) and with phosphatidylcholines (Bartus et al., 1982) have been reported to be negative or at least equivocal. Although not yet subject to clinical trials for treatment of AD, cytidine-5 -diphosphocholine, a major precursor in the synthesis of phosphatidylcholines, phosphati-dylserines and phosphatidylethanolamines in cell membranes, affects the synthesis and levels of cell membrane phospholipids in PC-12 cells when simultaneously incubated with choline (Lopez G.-Coviella and Wurtman, 1992) and in brain of mice after long-term treatment for 27 months (Lopez... 

Fig. 2.4 Diagram showing the effect of ischemic injury on glycerophospholipid-derived iipid mediators in brain. Plasma membrane (PM) iV-methyl-D-aspartate receptor (NMDA-R) giuteimate (GIu) phosphatidylcholine (PtdCho) lyso-phosphatidylcholine (lyso-PtdCho) cytosolic phospholipase A2 (CPLA2) secretory phospholipase A2 (SPLA2) cyclooxygenase (COX-2) arachidonic add (ARA) platelet-activating factor (RAF) 4-hydroxynonenal (4-HNE) reactive oxygen species (ROS) nuclear factor kappaB (NF-kB) nuclear factor kappaB response element (NF-kB-RE) inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-ip (IL-ip) interleukin-6 (IL-6) matrix metaUoproteinases (MMPs) positive sign (+) represents upregulation...

Fig. 7.9 Generation of JV-acylethanolamine (NAE) and A-acylphosphatidylethanolamine (NAPE) in brain. Phosphatidylcholine (PtdCho) phosphatidylethanolamine (PtdEtn) cannabinoid lecep-torl (CBj-R) JV-methyl-D-aspartate receptor (NMDA-R) tmandamide and 2-arachidonyl-gltcerol not only stimulate CBi-R but also have stabilizing effects on neural membranes. TBI increases the formation of NAE and NAPE. Ai-arachidonylethanolamine stimulate ceramide formation, N-acylethanolamine inhibit ceramidase. Ceramide induces apoptosis. Plus sign indicate stimulation and minus sign indicates inhibition, (f) Indicate increase in levels...

Because of its noninvasive nature, MRS is especially suited to in vivo studies of brain. Numerous cerebral metabolites are detectable, particularly with MRS (Figure 6). A few metabolites contribute prominent peaks and these are most easily quantifiable. Naa is predominantly found in the central nervous system, especially in neurons, although its functional role is not fully understood. Dynamic changes in brain Naa concentration have been observed reduced concentration may indicate neuronal dysfunction as well as loss. A prominent peak due to choline (Cho) has contributions from several metabolites including phosphorylcholine and glycerophosphorylcholine. Phosphatidylcholine is synthesized from chohne and is a major constituent of cell membranes being bound, this component is NMR invisible due to a very short T2. Pathologically increased membrane... 

Sugiura, Y., et al. (2009) Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. Journal of Lipid Research, 50,1776-1788. 

The use of liposomes for the transfer of therapeutic enzymes through the "blood-brain" barrier, which permits to deliver these enzymes into cells of the central nervous system also seems very attractive. It has been already shown that horse raddish peroxidase, encapsulated into liposomes made of phosphatidylcholine, cholesterol and phosphatidic acid (7 2 1 molar ratio), acquires the ability to cross the hemato-encephalic barrier, whereas the native enzyme cannot. The presence of peroxidase in brain cells was proved by histochemical methods. The same authors have shown that after injection of the liposomal glucose oxidase into the rat s tail vein, up to 5% of the enzymatic activity can be discovered in brain tissues. ... 

We describe the utility of intermediate-pressure MALDI and tandem mass spectrometry (MS/MS and MS ) for the characterization and imaging of phospholipids in brain tissue sections. The use of both MS/MS spectra and MS/MS images allows for identification of isobaric compounds. The structural characterization of phosphatidylcholines, phosphatidylserines, phosphatidylethanolamines, and sphingomyelins directly fi om tissue sections is described. 

The production of free inositol from phosphatidylinositol suggests the possibility that a phospholipase D type of activity might be involved in this system. The occurrence of phospholipase D in animal tissues was not reported until recently, when an enzyme which cleaves phosphatidylcholine to give choline and phosphatidic acid was found in brain tissue (Saito Kanfer, 1975). It is not known whether phosphatidylinositol can act as its substrate in an analogous reaction. 

The synthesis of phosphatidylcholine (Ptd-choline) in animal tissues is carried out chiefly by the cytidine nucleotide pathway, although base-exchange reaction and stepwise methylation of preexisting phosphatidylethanolamine (Ptd-ethanolamine) also contribute to its formation "7 The N-methylation pathway, first demonstrated in liver by Bremer and Greenberg and successively described in this tissue by several authors, has not been however unequivocally demonstrated in brain, and conflicting data have been produced in this c onnection, ... 

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