Hydrolysis of inositol phospholipids by phospholipase C is initiated by either receptor stimulation or opening of Ca2+ channels. This was once thought to be the sole mechanism to produce the diacylglycerol that links extracellular signals to intracellular events through activation of protein kinase C. It is becoming clear that agonist-induced hydrolysis of other membrane phospholipids, particularly choline phospholipids, by phospholipase D and phospholipase A2 may also take part in cell signaling. The products of hydrolysis of these phospholipids may enhance and prolong the activation of protein kinase C. Such prolonged activation of protein kinase C is essential for long-term cellular responses such as cell proliferation and differentiation.

https://science.sciencemag.org/content/sci/258/5082/607.full.pdf

Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C

Lipids of nervous tissue: composition and metabolism.

lcholine; PE, sn-3-phosphatidy lethanolamine; PG, sn -3-phosphatidylg lycerol; PI, sn -3-phosphatidyli nositol; SL, sulfolipid, sulfoquinovosyl­ diacylglycerol; TAG, triacylglycerol. (18: 1, 16: 0) OAG, etc denotes the specific acyl moieties esterified to the glycerol of the particular lipid. In the long-chain fatty acid shorthand the colon separates figures denoting the number of carbon atoms and the number of double bonds respectively in the molecule. Any additional figures following a period indicate the positions of the double bonds which are cis unless otherwise stated. 16:0, palmitic acid; (t) 16: 1, trans -hexadec-3-enoic acid; 18 :0, stearic acid; 18: 1, oleic acid (18 : 1.9); 18: 2, linoleic acid (18 : 2.9, 12); 18:3, a-linolenic acid (18:3.9, 12,15); 20: 1, icosa-l l-enoic acid (20: 1.11); 22: 1, erucic acid, docosa-13- enoic acid (22: 1.13); 22: 1.5, docosa-5-enoic acid.

Cellular organization of glycerolipid metabolism

Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders.

Once brain ischemia was induced in the gerbil cerebral fronto-parietal cortex, serial changes occurred in energy metabolites and various lipids. The amounts of inosi-tol-containing phospholipids began to decrease immediately after energy failure, followed by an increase in the amount of 1,2-diacylglycerol with a subsequent liberation of arachidonic acid and other free fatty acids. The fatty acid compositions of inositol-containing phospholipids, of 1,2-diacylglycerols produced by ischemia, and of free fatty acids liberated during ischemia were quite similar. The amount of stearic acid liberated was much larger than that of arachidonic acid between 30 s and 1 min of ischemia. On the other hand, there was no significant decrease in the amount of the other phospholipids except for phosphatidic acid. Furthermore, there was also no change in the fatty acid composition of phosphatidylcholine or phosphatidylethanol-amine throughout 15 min of ischemia. The amount of cytidine-monophosphate reached a peak (36.7 nmol/g wet wt) at 2 min of ischemia. These results indicated that arachidonic acid was predominantly liberated from inositol-containing phospholipids by phospholipase C, and by the diglyceride lipase and monoglyceride lipase system rather than from phosphatidylcholine or phosphatidylethanolam-ine by phospholipase A2 or plasmalogenase or choline phos-photransferase during the early period of ischemia.

Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex.

The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine.

The de novo biosynthesis of platelet-activating factor in rat brain.

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[Methyl-3H]choline has been injected intraventricularly into adult rabbits, and the rate of synthesis of phosphatidylcholine, choline plasmalogen and sphingomyelin (and their hydrosoluble precursors) in isolated neuronal and glial cells has been investigated. At all time intervals examined, the injected radioactivity was incorporated only into the base moiety of the choline lipids in both cell types. Maximum labelling of the two choline phosphoglycerides occurred in neurons 150 min after administration, whereas the highest specific radioactivity for glial phosphatidylcholine and choline plasmalogen was reached at 6 and 10 h, respectively. At any time interval examined, the neuronal and glial choline plasmalogen displayed a higher specific radioactivity than the corresponding diacyl-derivative. The two phosphoglycerides incorporated the base in both cell populations at a faster rate than did whole brain tissue. Sphingomyelin was labelled in both cells at a low rate and acquired measurable radioactivity levels only after 2 h from isotope administration.



Highest levels of radioactivity for phosphorylcholine and cytidine-5′-diphosphocholine were reached in both neurons and glia 1-2 h after administration, but these levels per unit protein were higher in glial than in neuronal cells.

The metabolism of labelled choline in neuronal and glial cells of the rabbit in vivo.

Several reports have indicated that platelet-activating factor (PAF) may play a role in the physiopathology of nervous tissue. We previously have demonstrated the presence, in the microsomal fractions of rat brain, of a phosphocholinetransferase which is able to synthesize PAF by thede novo pathway. The presence of dithiothreitol in the medium increases the rate of PAF biosynthesis, whereas it inhibits the synthesis of long-chain alkylacyl- and diacyl-glycerophosphocholines (GPC), including dioctanoyl-GPC. This and other properties, such as pH dependence and thermal stability, indicate that rat brain may have two distinct enzymes for the synthesis of PAF and other choline phospholipids. The affinity of these enzymes for CDPcholine is similar to that reported for other tissues, the Km being 42 μm and 55 μm with alkylacetylglycerol and dioctanoylglycerol as lipid substrates, respectively. The Vmax values were 3.0 and 2.2 nmol/mg prot/min for PAF and dioctanoyl-GPC, respectively. In addition, it was shown that the microsomal fraction of rat brain contains an acetyltransferase which can convert lysoPAF to PAF. Since it has been reported previously that brain tissue possesses phospholipase A2 activity that can hydrolyze alkylacyl-GPC to lysoPAF, we conclude that brain tissue has all enzymic activities for the synthesis of PAF by the “remodeling pathway”. The role of the two routes of PAF biosynthesis in nervous tissue remains to be established.

Properties of PAF-synthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain.

Grassi, Silvarosa, Ermelinda Francescangeli, Gianfrancesco Goracci, and Vito E. Pettorossi. Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei. J. Neur...

Ermelinda Francescangeli

Papers

The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine.

The de novo biosynthesis of platelet-activating factor in rat brain.

The metabolism of labelled choline in neuronal and glial cells of the rabbit in vivo.

Properties of PAF-synthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain.

Role of Platelet-Activating Factor in Long-Term Potentiation of the Rat Medial Vestibular Nuclei