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International Journal of Molecular... Jul 2022The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of... (Review)
Review
The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.
Topics: Atherosclerosis; Chronic Pain; Humans; Lipoproteins, LDL; Lysophosphatidylcholines; Phospholipases A2; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 35955410
DOI: 10.3390/ijms23158274 -
Glia Feb 2018For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous...
For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents. Interestingly, following its injection into white matter, LPC was cleared within 24 hr but by five days there was an elevation of endogenous LPC that was not associated with damage. This elevation of LPC in the absence of injury raises the possibility that the brain has mechanisms to buffer LPC. In support, LPC injury in culture was significantly ameliorated by albumin buffering. These results shed light on the mechanisms of LPC injury and homeostasis.
Topics: Animals; Cells, Cultured; Demyelinating Diseases; Female; Injections, Intraventricular; Lysophosphatidylcholines; Membrane Lipids; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelin Sheath; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 29068088
DOI: 10.1002/glia.23245 -
Thrombosis and Haemostasis Aug 2019
Topics: Blood Platelets; Cardiovascular Diseases; Cell-Derived Microparticles; Humans; Lysophosphatidylcholines
PubMed: 31266081
DOI: 10.1055/s-0039-1693024 -
The Journal of Organic Chemistry Jun 2022Lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) are important membrane constituents implicated in signaling and immune regulation. Synthesis of LPCs is...
Lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) are important membrane constituents implicated in signaling and immune regulation. Synthesis of LPCs is challenging due to rapid acyl migration, e.g., induced by chromatography. We here report a highly regioselective synthesis of LPC and mixed PC via an intermediate allowing specific terminal acyl introduction, yielding the pure LPC without chromatography by an exceedingly mild TBS deprotection, using 1 equiv of TFA in aqueous solution. The method enabled the synthesis of glycerol-, acyl-, and choline-labeled LPC.
Topics: Lysophosphatidylcholines; Phosphatidylcholines; Water
PubMed: 35649118
DOI: 10.1021/acs.joc.2c00335 -
Antimicrobial Agents and Chemotherapy Nov 2020Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of...
Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of and at least two other Gram-negative bacteria This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.
Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Lysophosphatidylcholines; Microbial Sensitivity Tests; Polymyxin B
PubMed: 32988824
DOI: 10.1128/AAC.01337-20 -
Acta Poloniae Pharmaceutica 2014For many years the role of lysophospholipids (LPLs) was associated only with structural and storage components of the cell without any informational function. Today,... (Review)
Review
For many years the role of lysophospholipids (LPLs) was associated only with structural and storage components of the cell without any informational function. Today, based on many research projects performed during the last decades, it is clear that some of the LPLs act as hormone-like signaling molecules and thus are very important inter- and intracellular lipid mediators. They can activate specific membrane receptors and/or nuclear receptors regulating many crucial physiological and pathophysiological processes. The LPLs were iden- tified as involved in a majority of cellular processes, including modulation of disease-related mechanisms observed, for instance, in case of diabetes, obesity, atherosclerosis and cancer. Among LPLs, lysophosphatidylcholine (LPC) and lysophosphatidylinositol (LPI) are becoming attractive research topics. Their recently revealed activities as novel ligands of orphan G protein-coupled receptors (i.e., GPR55 and GPR119) involved in modulation of tumor physiology and insulin secretion seem to be one of the most interesting aspects of these compounds. Moreover, the most recent scientific reports emphasize the significance of the acyl chain structure bound to the glycerol basis of LPL, as it entails different biological properties and activities of the compounds.
Topics: Animals; Diabetes Mellitus; Humans; Ligands; Lysophosphatidylcholines; Lysophospholipids; Neoplasms; Receptors, Cannabinoid; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 25745761
DOI: No ID Found -
Journal of the European Academy of... Jul 2023Although abnormal metabolism plays a critical role in the pathogenesis of psoriasis, the details are unclear.
BACKGROUND
Although abnormal metabolism plays a critical role in the pathogenesis of psoriasis, the details are unclear.
OBJECTIVES
Here, we identified to explore the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis.
METHODS
The level of LPC in plasma and skin lesions and the expression of G2A on skin lesions of psoriasis patients were detected by enzyme-linked immunosorbent assay, liquid chromatography-tandem mass spectrometry, or immunohistochemistry, respectively. The glycolysis in the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model was detected by extracellular acidification rate. LPC was subcutaneously injected into IMQ-treated mouse ears, and the phenotype as well as the glycolysis were evaluated. Exploring the effects and mechanism of LPC on keratinocytes and CD4 T cells by culturing primary keratinocytes and CD4 T in vitro.
RESULTS
We found that LPC was significantly increased both in the plasma and skin lesions of psoriatic patients, while G2A, exerting an essential role in LPC-inducing biological functions, was increased in psoriatic lesions. The abundance of LPC was positively correlated with glycolytic activity in the psoriasis-like mouse model. LPC treatment facilitated psoriasis-like inflammation and glycolytic activity in skin lesions. Mechanistically, the LPC/G2A axis significantly triggered glycolytic activity and produced inflammatory factors in keratinocytes, and blockade of glycolysis abrogated LPC-induced expression of inflammatory mediators in keratinocytes. LPC activated STAT1, resulting in recognition and binding to the promoters of GCK and PKLR, which are glycolytic rate-limiting enzymes. Furthermore, the LPC/G2A axis directly benefited Th1 differentiation, which was dependent on LPC-induced glycolytic activity. Notably, LPC indirectly facilitated Th17 differentiation by inducing the secretion of IL-1β in keratinocytes-T cells coculture system.
CONCLUSIONS
Taken together, our findings revealed the role of the LPC/G2A axis in the pathogenesis of psoriasis; targeting LPC/G2A is a potential strategy for psoriasis therapy.
Topics: Mice; Animals; Lysophosphatidylcholines; Psoriasis; Keratinocytes; Imiquimod; Skin Diseases; Cell Differentiation; Disease Models, Animal; Mice, Inbred BALB C; Skin
PubMed: 37013729
DOI: 10.1111/jdv.19088 -
Clinical and Translational Medicine Jan 2023Lung cancer is a widespread malignancy with a high death rate and disorder of lipid metabolism. Lysophosphatidylcholine (lysoPC) has anti-tumour effects, although the...
Lung cancer is a widespread malignancy with a high death rate and disorder of lipid metabolism. Lysophosphatidylcholine (lysoPC) has anti-tumour effects, although the underlying mechanism is not entirely known. The purpose of this study aims at defining changes in lysoPC in lung cancer patients, the effects of lysoPC on lung cancer cells and molecular mechanisms. Lung cancer cell sensitivity to lysoPC was evaluated and decisive roles of long-chain acyl-coenzyme A synthase 5 (ACSL5) in lysoPC regulation were defined by comprehensively evaluating transcriptomic changes of ACSL5-downregulated epithelia. ACSL5 over-expressed in ciliated, club and Goblet cells in lung cancer patients, different from other lung diseases. LysoPC inhibited lung cancer cell proliferation, by inducing mitochondrial dysfunction, altering lipid metabolisms, increasing fatty acid oxidation and reprograming ACSL5/phosphoinositide 3-kinase/extracellular signal-regulated kinase-regulated triacylglycerol-lysoPC balance. Thus, this study provides a general new basis for the discovery of reprogramming metabolisms and metabolites as a new strategy of lung cancer precision medicine.
Topics: Humans; Cell Proliferation; Fatty Acids; Lung Neoplasms; Lysophosphatidylcholines; Phosphatidylinositol 3-Kinases; Coenzyme A Ligases
PubMed: 36639836
DOI: 10.1002/ctm2.1180 -
Current Medicinal Chemistry 2007Lysophosphatidylcholine (LPC) is a bioactive proinflammatory lipid generated by pathological activities. LPC is also a major phospholipid component of oxidized... (Review)
Review
Lysophosphatidylcholine (LPC) is a bioactive proinflammatory lipid generated by pathological activities. LPC is also a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL) and is implicated as a critical factor in the atherogenic activity of Ox-LDL. LPC is believed to play an important role in atherosclerosis and inflammatory diseases by altering various functions in a number of cell-types, including endothelial cells, smooth muscle cells, monocytes, macrophages, and T-cells. LPC activates several second messengers -- including protein kinase C, extracellular-signal-regulated kinases, protein tyrosine kinases, and Ca(2+) -- implicating the engagement of transduction mechanisms in its observed actions. Moreover, recent evidence suggests that in several cell-types, cloned orphan G-protein-coupled receptors may serve as the specific receptors via which LPC modulates second messenger pathways (although LPC may not be a direct ligand of such receptors). In addition, current evidence suggests that LPC impairs the endothelium-dependent relaxations mediated by endothelium-derived relaxing factors and directly modulates contractile responses in vascular smooth muscle. However, despite all this, and although elevated levels of LPC have been linked to the cardiovascular complications associated with atherosclerosis, ischemia, and diabetes, the precise pathophysiological roles played by LPC in several states remain to be established. In this review, we focus in some detail on the entirety of the signal-transduction system for LPC, its pathophysiological implications, and the vascular abnormalities associated with it.
Topics: Atherosclerosis; Endothelium, Vascular; Humans; Lysophosphatidylcholines; Signal Transduction
PubMed: 18220755
DOI: 10.2174/092986707782793899 -
Nutrition Reviews Jan 1990
Review
Topics: Animals; Choline Deficiency; Kidney; Lysophosphatidylcholines; Phosphatidylcholines; Rats
PubMed: 2186314
DOI: 10.1111/j.1753-4887.1990.tb02876.x