In vivo synthesis of phosphatidylcholine in rat brain via the phospholipid methylation pathway

Lakher, Michael; Wurtman, Richard J.

doi:10.1016/0006-8993(87)90576-2

Cited by 16 publications

(5 citation statements)

References 30 publications

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“…If de novo PE synthesis is stimulated in cholinergic neurons, increased de novo choline synthesis could also occur via the transmethylation of PE to phosphatidylcholine with subsequent hydrolysis of the lipid to produce choline (Kewitz and Pleul, 1976;Lakher and Wurtman, 1987). If EA and PEA were enhancing ACh synthesis by increasing choline content then the addition of choline itself should mimic this effect.…”

Section: Discussionmentioning

confidence: 99%

“…EA is incorporated into phosphatidylethanolamine (PE) via the formation of two intermediate compounds, PEA and cytidine 5'-diphosphoethanolamine (CDP-EA) (Kennedy and Weiss, 1956). Furthermore, PEA and PE can be sequentially methylated in the brain to yield phosphocholine, PC, and choline (Kewitz and Pleul, 1976;Lakher and Wurtman, 1987). The effects of these various compounds on ACh synthesis were, therefore, measured.…”

Section: Effect Of Ea-derived Compounds On Ach Synthesismentioning

confidence: 99%

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Purification and Characterization of a Central Cholinergic Enhancing Factor from Rat Brain: Its Identity as Phosphoethanolamine

Bostwick

Landers

Crawford

et al. 1989

Journal of Neurochemistry

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A compound that can enhance the apparent synthesis of acetylcholine in cultured explants of the medial septal nucleus has been purified from rat brain and identified as phosphoethanolamine. Acetylcholine synthesis is stimulated two- to threefold in cultures grown for 5 days in the presence of phosphoethanolamine, ethanolamine, or cytidine 5'-diphosphoethanolamine at concentrations above 100 microM. This effect appears to result from an increase in the accumulation of choline via the high-affinity, sodium-dependent uptake mechanism. The development of choline acetyltransferase activity is not affected. Phosphoethanolamine and ethanolamine seem to enhance the ability of developing cholinergic neurons to utilize choline accumulated via the sodium-dependent high-affinity choline uptake mechanism for the preferential production of acetylcholine without increasing the general metabolism of the cultures. Choline itself and its related derivatives are not stimulatory for these effects.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Ea-derived Compounds On Ach Synthesismentioning

confidence: 99%

Purification and Characterization of a Central Cholinergic Enhancing Factor from Rat Brain: Its Identity as Phosphoethanolamine

Bostwick

Landers

Crawford

et al. 1989

Journal of Neurochemistry

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“…Choline is an essential nutrient for mammals, including humans, and consequently most of the Choline used for ACh synthesis derives from the diet, whereas a smaller fraction is synthesized de novo [103] predominantly by the liver [104][105] but additionally in situ by brain cells [106][107] including cholinergic neurons [108]. The dietderived and endogenously synthesized circulating Choline enters the brain via blood -brain barrier transporters [109][110].…”

Section: C-non-neuronal Cholinergic Systemmentioning

confidence: 99%

Development of Novel Therapeutic Strategies for Lung Cancer: Targeting the Cholinergic System

Russo¹,

Catassi²,

Cesario³

et al. 2006

CMC

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One of the earliest descriptions of non-neuronal ACh synthesis was by Morris who reported that ACh was synthesized in the placenta [1]; furthermore, Falugi et al. showed the presence of AChE in human fibrosarcoma cells [2]. Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3-16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phenotype and that ACh exerts as an autocrine growth factor in human lung tumours [16]. Moreover, it has been recently reported that nicotine in lung adenocarcinoma A549 cells, potently induces Bad phosphorylation at serine (S)112, S136 and S155 in a mechanism involving activation of MAPKs, ERK1/2, PI3K/AKT and PKA through the linking to alpha7-receptors [9]. Bad phosphorylation results in sequestering Bad from mitochondria and subsequently interacting with 14-3-3 in the cytosol [9]. We have recently reported that human malignant pleural mesothelioma expresses a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) have a proliferative effect and antagonists (i.e. curare or alpha-cobratoxin) have an inhibitory effect. Furthermore apoptosis mechanisms are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-kappaB complexes and phosphorylation of Bad at S112, curare proapoptotic via G0-G1 arrest p21waf-1-dependent, but p53-independent) [16]. The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and opens up new translational research strategies.

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“…Because the rate-limiting factor in the synthesis of ACh is thought to be the supply of its precursor, choline (for review, see Blusztajn and Wurtman, 1983), such a compensatory mechanism might entail an increased delivery of choline to ChAT. Choline is an essential nutrient for mammals, including humans (Food and Nutrition Board, 1998), and consequently most of the choline used for ACh synthesis derives from the diet, whereas a smaller fraction is synthesized de novo (Blusztajn and Wurtman, 1983) predominantly by the liver (Walkey et al, 1997;Watkins et al, 2003) but additionally in situ by brain cells (Blusztajn and Wurtman, 1981;Lakher and Wurtman, 1987), including cholinergic neurons (Blusztajn et al, 1987). The diet-derived and endogenously synthesized circulating choline enters the brain via a blood-brain barrier transporter (Pardridge and Oldendorf, 1977;Klein et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Choline Transporter 1 Maintains Cholinergic Function in Choline Acetyltransferase Haploinsufficiency

Brandon¹,

Mellott²,

Pizzo³

et al. 2004

J. Neurosci.

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Choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine (ACh), is thought to be present in kinetic excess in cholinergic neurons. The rate-limiting factor in ACh production is the provision of choline to ChAT. Cholinergic neurons are relatively unique in their expression of the choline transporter 1 (CHT1), which exhibits high-affinity for choline and catalyzes its uptake from the extracellular space to the neuron. Multiple lines of evidence indicate that the activity of CHT1 is a key determinant of choline supply for ACh synthesis. We examined the interaction of ChAT and ChT activity using mice heterozygous for a null mutation in the Chat gene (Chatϩ/Ϫ). In these mice, brain ChAT activity was reduced by 40 -50% relative to the wild type, but brain ACh levels as well as ACh content and depolarization-evoked ACh release in hippocampal slices were normal. However, the amount of choline taken up by CHT1 and ACh synthesized de novo from choline transported by CHT1 in hippocampal slices, as well as levels of CHT1 mRNA in the septum and CHT1 protein in several regions of the CNS, were 50 -100% higher in Chatϩ/Ϫ than in Chatϩ/ϩ mice. Thus, haploinsufficiency of ChAT leads to an increased expression of CHT1. Increased ChT activity may compensate for the reduced ChAT activity in Chatϩ/Ϫ mice, contributing to the maintenance of apparently normal cholinergic function as reflected by normal performance of these mice in several behavioral assays.

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In vivo synthesis of phosphatidylcholine in rat brain via the phospholipid methylation pathway

Cited by 16 publications

References 30 publications

Purification and Characterization of a Central Cholinergic Enhancing Factor from Rat Brain: Its Identity as Phosphoethanolamine

Purification and Characterization of a Central Cholinergic Enhancing Factor from Rat Brain: Its Identity as Phosphoethanolamine

Development of Novel Therapeutic Strategies for Lung Cancer: Targeting the Cholinergic System

Choline Transporter 1 Maintains Cholinergic Function in Choline Acetyltransferase Haploinsufficiency

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