Lysophosphatidylcholine Drives Neuroblast Cell Fate

Paoletti, Luciana; Domizi, Pablo; Marcucci, Hebe; Montaner, Aneley; Krapf, Darío; Salvador, Gabriela Alejandra; Banchio, Claudia

doi:10.1007/s12035-015-9528-0

Cited by 16 publications

(24 citation statements)

References 84 publications

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“…We have previously demonstrated that cytidine triphosphate (CTP):phosphocholine cytidylyltransferase (CCTα) or choline kinase (CKα) overexpression enhances phosphatidylcholine (PtdCho) biosynthesis in neuroblastoma Neuro-2a cells and induces neuronal differentiation in the absence of retinoic acid 11 . This suggested role of PtdCho as a positive regulator of neuronal cell fate was further confirmed by demonstrating that lysophosphatidylcholine turns on neuronal differentiation by activation of the small G protein Ras and by triggering the Raf/MEK/ERK pathway 8 .…”

Section: Introductionmentioning

confidence: 75%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.

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Section: Introductionmentioning

confidence: 75%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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“…Previous studies have shown that some LysoPLs can induce or suppress neuronal differentiation (16:0 LPC and 16:0 LPA, respectively) in Neuro2a cells (17). Both of these species are present in FBS, suggesting the possibility that the conditions used to induce differentiation in the cells (a decrease in FBS content in the culture medium from 10% to 2%) resulted in changes in their levels that contributed to the differentiation process.…”

Section: Neuronal Differentiation Is Increased In Lypla Ko Cellsmentioning

confidence: 99%

“…The consequences of ERK phosphorylation have been extensively studied and are dependent on cell type. In neuroblastoma cells, the MAPK signaling pathway is known to induce neuronal differentiation, increasing neurite outgrowth and cell area and initiating gap junction intracellular communication (16)(17)(18)(19). To assess the impact of MAPK signaling pathway activation in the context of LYPLA deficiency, we utilized immunocytochemistry and high-throughput imaging to compare the morphology and degree of neuronal differentiation between the WT and Lypla KO Neuro2a cells.…”

Section: Neuronal Differentiation Is Increased In Lypla Ko Cellsmentioning

confidence: 99%

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Lysophospholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling

Wepy

Galligan

Kingsley

et al. 2019

Journal of Lipid Research

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This article is available online at http://www.jlr.org ture, shape, and fluidity of cell membranes (1)(2)(3). Each LysoPL comprises one nonpolar acyl chain, varying in length and degree of unsaturation, and a polar glycerophosphate headgroup. Based on the structure of the headgroup, LysoPLs belong primarily to one of six classes, including lysophosphatidic acids (LPAs), lysophosphatidylcholines (LPCs), lysophosphatidylethanolamines (LPEs), lysophosphatidylglycerols (LPGs), lysophosphatidylinositols (LPIs), and lysophosphatidylserines (LPSs), each with distinct biological functions dependent on physiological location and availability of their respective cellular receptors.LysoPLs have been shown to elicit a wide range of biological effects, including cell proliferation, intracellular calcium mobilization, metabolic activity, inflammatory and antiinflammatory processes, and neuritogenesis (4-20). These effects are generally evoked through ligand-receptor interactions, but this is not always the case. For example, high physiological concentrations of LPCs (200 µM in human plasma) call into question a receptor agonist role in some circumstances, and accruing evidence supports the hypothesis that they can elicit effects by altering membrane properties or interacting directly with proteins in ways other than saturable binding to a specific site (21-24). Abstract Lysophospholipids (LysoPLs) are bioactive lipid species involved in cellular signaling processes and the regulation of cell membrane structure. LysoPLs are metabolized through the action of lysophospholipases, including lysophospholipase A1 (LYPLA1) and lysophospholipase A2 (LYPLA2).A new X-ray crystal structure of LYPLA2 compared with a previously published structure of LYPLA1 demonstrated nearidentical folding of the two enzymes; however, LYPLA1 and LYPLA2 have displayed distinct substrate specificities in recombinant enzyme assays. To determine how these in vitro substrate preferences translate into a relevant cellular setting and better understand the enzymes' role in LysoPL metabolism, CRISPR-Cas9 technology was utilized to generate stable KOs of Lypla1 and/or Lypla2 in Neuro2a cells. Using these cellular models in combination with a targeted lipidomics approach, LysoPL levels were quantified and compared between cell lines to determine the effect of losing lysophospholipase activity on lipid metabolism. This work suggests that LYPLA1 and LYPLA2 are each able to account for the loss of the other to maintain lipid homeostasis in cells; however, when both are deleted, LysoPL levels are dramatically increased, causing phenotypic and morphological changes to the cells.-Wepy, pholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling. J. Lipid Res. 2019. 60: 360-374.Supplementary key words brain lipids • eicosanoids • prostaglandins • fatty acid • protein kinases/MAP kinase • lipidomics • mass spectrometry • fluorescence microscopy • neurons • X-ray crystallography Lysophospholipids (LysoPLs) are detergent-like lipid species that play a c...

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“…Additional specific functions of the neuronal membrane include nerve impulse conduction and neurotransmission [5]. In the Central Nervous System (CNS) there are various conditions involving phospholipids that can lead to an impairment of functions [6], such as brain maturation [7][8][9][10], neurite growth and neuronal regeneration [11]. Impaired phospholipid metabolism has been implicated in the development of traumatic brain injury (TBI) [12][13][14][15][16][17][18][19][20][21] and cerebral ischemia [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Citicoline in the Treatment of Cognitive Impairment

Secades¹

2019

J Neurol Exp Neurosci

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Vascular cognitive impairment is a process which is more frequent in patients with cardiovascular risk factors. The etiology of this kind of impairment could be related to different types of cerebrovascular disorders, given that silent cerebral infarctions or microinfarcts, correlated with small vessel disease, are one of the principal etiologies. Microinfarcts, associated with small vessel diseases, should be considered one of the possible causes of clinical suspicion in patients with cardiovascular risk factors who are asking for help for cognitive complaints. Among the proposed treatments for cognitive impairment there is citicoline. This is an updated review of the possible use of citicoline in the treatment of cognitive impairment.

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Lysophosphatidylcholine Drives Neuroblast Cell Fate

Cited by 16 publications

References 84 publications

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Lysophospholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling

Citicoline in the Treatment of Cognitive Impairment

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