Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner

Drzazga, Anna; Sowińska, Anna; Krzemińska, Agnieszka; Rytczak, Przemysław Piotr; Koziołkiewicz, Maria; Gendaszewska‐Darmach, Edyta

doi:10.1016/j.bbrc.2017.05.145

Cited by 28 publications

(20 citation statements)

References 40 publications

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“…Moreover, we speculate that lyso-type phospholipids could also have a potential role, altering intracellular calcium fluxes through G-protein-coupled receptors (GPR), and thus promote cell migration and proliferation as described for mammal tumorigenic cells (Drzazga et al, 2017;. On the other hand, late stages of the limb regeneration present an enhanced catabolism, evidenced by low levels of several phospholipids and a high abundance of various dipeptides.…”

Section: Discussionmentioning

confidence: 83%

Functional Characterization of the Lin28/let-7 Circuit during Forelimb Regeneration inAmbystoma mexicanumand its Influence on Metabolic Reprogramming

Varela-Rodríguez

Abella-Quintana

Varela-Rodríguez

et al. 2020

Preprint

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The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored.However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.The Axolotl Lin28/let-7 Circuit 3 Pioneer studies have related some components of the Lin28/let-7 circuit with regenerative processes, as those that report a high regenerative plasticity in juvenile stages of Caenorhabditis elegans, where immature neurons with low levels of mature let-7 retain a robust regeneration at the axon disruption site, nearby to neural body (Nix and Bastiani, 2013;Zou et al., 2013). Similarly, the transient overexpression of Lin28 in postnatal sensory neurons of mouse after injury, induce an axonal regeneration in vivo through changes in the balance of the AKT-mTOR pathway (Wang et al., 2018).Therefore, an adequate cell metabolic state is relevant for regeneration, since the AKT-mTOR pathway acts as an important mediator between anabolic and catabolic cell reactions (Altomare and Khaled, 2012;Saxton and Sabatini, 2017). In this sense, it has been shown that the inducible overexpression of Lin28A in mouse neonatal tissues, improves regeneration by a rewiring of the primary energetic metabolism, where the glycolysis is favored to increase intermediary metabolites of the Krebs cycle (Shyh-Chang et al., 2013). However, such metabolic reprogramming of the cell bioenergetics differs from other metabolic profiles also achieved with overexpression of Lin28A, but in the context of embryonic development, or during active proliferation of primed pluripotent stem cells and malignant neoplastic cells (Ma et al., 2014;Miyazawa et al., 2017;Zhang et al., 2016).Since the role of the Lin28/let-7 circuit has not been directly studied in the context of epimorphosis, using an amphibian model with a high and innate regenerative capacity, we decided to characterize its behavior and function during forelimb regeneration in axolotl (Ambystoma mexicanum). In this study, we describe the spatio-temporal expression dynamics of ...

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Section: Discussionmentioning

confidence: 83%

Functional Characterization of the Lin28/let-7 Circuit during Forelimb Regeneration inAmbystoma mexicanumand its Influence on Metabolic Reprogramming

Varela-Rodríguez

Abella-Quintana

Varela-Rodríguez

et al. 2020

Preprint

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“…We have shown that phosphorothioate analogues of LPCs did not lead to significant cAMP increase but stimulated intracellular Ca 2+ via GPR119-dependent manner [24]. GPR55 is another GPCR target for LPCs [30]. Both GPR119 and GPR55 receptors are also stimulated by endocannabinoids [14], but GPR55 is a well-documented target for lysophosphatidylinositol, which structurally resembles LPC [39].…”

Section: Introductionmentioning

confidence: 92%

“…We have recently shown that LPC bearing oleoyl (18:1) and palmitoyl (16:0) fatty acid residue facilitate glucose stimulated insulin secretion (GSIS) from pancreatic cells. Those two LPC moieties recognize not only the previously discovered GPR119 receptor [29] but also GPR40 and GPR55 [24,30] which represent a totally novel antidiabetic approach. GPR40, activated mainly by medium-and long-chain free fatty acids (FFA) [31], is predominately expressed in insulin-secreting pancreatic β-cells and enteroendocrine L, K, and I-cells [32].…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidylcholine Containing Anisic Acid Is Able to Stimulate Insulin Secretion Targeting G Protein Coupled Receptors

et al. 2020

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Diabetes mellitus is a worldwide health problem with high rates of mortality and morbidity. Management of diabetes mellitus by dietary components is achievable especially at the initial stage of the disease. Several studies confirmed the antidiabetic activities of simple phenolic acids and lysophosphatidylcholine (LPC). The main goal of this study was to identify new potential insulin secretion modulators obtained by combining the structures of two natural compounds, namely O-methyl derivatives of phenolic acids and phospholipids. LPC and phosphatidylcholine bearing methoxylated aromatic carboxylic acids were tested as potential agents able to improve glucose-stimulated insulin secretion (GSIS) and intracellular calcium mobilization in MIN6 β pancreatic cell line. Our results show that LPC with covalently bonded molecule of p-anisic acid at the sn-1 position was able to induce GSIS and intracellular calcium flux. Notably, 1-anisoyl-2-hydroxy-sn-glycero-3-phosphocholine did not affect the viability of MIN6 cells, suggesting its potential safe use. Furthermore, we have shown that three G protein coupled receptors, namely GPR40, GPR55, and GPR119, are targeted by this LPC derivative.

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“…Next, we asked if CID 16020046, a GPR55 antagonist (32,33), enhances cell proliferation in size-restricted salispheres. Exposing salispheres to CID 16020046 (1 μM) for 6 days induced significant cellular expansion, as measured by the number of Hoechst + nuclei, as compared with vehicle-treated controls (Figure 4D).…”

Section: Gpr55 Expression In Human and Mouse Salivary Glandsmentioning

confidence: 99%

GPR55 controls functional differentiation of self-renewing epithelial progenitors for salivation

Korchynska

Lutz²,

Borók

et al. 2019

JCI Insight

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Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner

Cited by 28 publications

References 40 publications

Functional Characterization of the Lin28/let-7 Circuit during Forelimb Regeneration inAmbystoma mexicanumand its Influence on Metabolic Reprogramming

Functional Characterization of the Lin28/let-7 Circuit during Forelimb Regeneration inAmbystoma mexicanumand its Influence on Metabolic Reprogramming

Lysophosphatidylcholine Containing Anisic Acid Is Able to Stimulate Insulin Secretion Targeting G Protein Coupled Receptors

GPR55 controls functional differentiation of self-renewing epithelial progenitors for salivation

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