• Biomolecules & Therapeutics
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• 제16권2호
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• pp.69-76
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• 2008

Lysophosphatidylcholine (LPC) is an endogenous phospholipid. LPC has various stimulating or modulating activities on immune cells, including lymphocytes, monocytes/macrophages and neutrophils. Studies generally revealed pro-inflammatory activities of LPC, but accumulating evidence indicates that LPC has also anti-inflammatory actions. Here we summarize immunomodulatory actions of LPC.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.175-182
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• 2022

Translocation of azurophil granules is pivotal for bactericidal activity of neutrophils, the first-line defense cells against pathogens. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances bactericidal activity of human neutrophils via increasing translocation of azurophil granules. However, the precise mechanism of LPC-induced azurophil granule translocation was not fully understood. Treatment of neutrophil with LPC significantly increased CD63 (an azurophil granule marker) surface expression. Interestingly, cytochalasin B, an inhibitor of action polymerization, blocked LPC-induced CD63 surface expression. LPC increased F-actin polymerization. LPC-induced CD63 surface expression was inhibited by both a Rho specific inhibitor, Tat-C3 exoenzyme, and a Rho kinase (ROCK) inhibitor, Y27632 which also inhibited LPC-induced F-actin polymerization. LPC induced Rho-GTP activation. NSC23766, a Rac inhibitor, however, did not affect LPC-induced CD63 surface expression. Theses results suggest a novel regulatory mechanism for azurophil granule translocation where LPC induces translocation of azurophil granules via Rho/ROCK/F-actin polymerization pathway.

• BMB Reports
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• 제50권6호
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• pp.323-328
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• 2017

Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein (ox-LDL) and is implicated in its atherogenic activity. This study investigated the effects of LPC on cell viability, intracellular calcium homeostasis, and the protective mechanisms of chlorogenic acid (CGA) in human umbilical vein endothelial cells (HUVECs). LPC increased intracellular calcium ($[Ca^{2+}]_i$) by releasing $Ca^{2+}$ from intracellular stores and via $Ca^{2+}$ influx through store-operated channels (SOCs). LPC also increased the generation of reactive oxygen species (ROS) and decreased cell viability. The mRNA expression of Transient receptor potential canonical (TRPC) channel 1 was increased significantly by LPC treatment and suppressed by CGA. CGA inhibited LPC-induced $Ca^{2+}$ influx and ROS generation, and restored cell viability. These results suggested that CGA inhibits SOC-mediated $Ca^{2+}$ influx and ROS generation by attenuating TRPC1 expression in LPC-treated HUVECs. Therefore, CGA might protect endothelial cells against LPC injury, thereby inhibiting atherosclerosis.

• Biomolecules & Therapeutics
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• 제15권1호
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• pp.52-57
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• 2007

Lysolipids such as lysophosphatidylcholine (LPC), sphingosylphosphorylcholine (S PC), galactosylsphingosine (psychosine) have been matched as ligands for OGR1-subfamily G-protein-coupled receptors (GPCR), consisted of OGR1, GPR4, G2A, and TDAG8. Recently, those members of GPCRS have been reported as proton-sensing GPCRs. We used Jurkat T cells, which express four members of OGR1 subfamily GPCRs endogenously to investigate effects of proton on lysolipid-induced several cellular events. We found no significant effect of proton on the lysolipid-induced $Ca^{2+}$ increase and ROS production in Jurkat T cells. Further investigation is necessary to clarify the relationship of lysolipid and proton on the OGR1-subfamily GPCRs.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.93-99
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• 2002

Effects of oxidized low-density lipoprotein (ox-LDL), $1-{\alpha}-stearoyl-lysophosphatidylcholine$ (LPC), on intracellular $Ca^{2+}$ concentration were examined in mouse endothelial cells by measuring intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ with fura 2-AM and reverse transcription-polymerase chain reaction (RT-PCR). LPC increased $[Ca^{2+}]_i$ under the condition of 1.5 mM $[Ca^{2+}]_o$ but did not show any effect under the nominally $Ca^{2+}-free$ condition. Even after the store depletion with $30{\mu}M$ 2,5-di-tert- butylhydroquinone (BHQ) or $30{\mu}M$ ATP, LPC could still increase the $[Ca^{2+}]_i$ under the condition of 1.5 mM $[Ca^{2+}]_o.$ The time required to increase [$Ca{2+}$]i (about 1 minute) was longer than that for ATP-induced $[Ca^{2+}]_i$ increase $(10{\sim}30\;seconds).$ LPC-induced $[Ca^{2+}]_i$ increase was completely blocked by $1{\mu}M\;La^{3+}.$ Transient receptor potential channel(trpc) 4 mRNA was detected with RT-PCR. From these results, we suggest that LPC increased $[Ca^{2+}]_i$ via the increase of $Ca^{2+}$ influx through the $Ca^{2+}$ routes which exist in the plasma membrane.

• Molecules and Cells
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• 제20권3호
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• pp.429-434
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• 2005

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

• Molecules and Cells
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• 제43권3호
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• pp.286-297
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• 2020

Mammalian patatin-like phospholipase domain containing proteins (PNPLAs) play critical roles in triglyceride hydrolysis, phospholipids metabolism, and lipid droplet (LD) homeostasis. PNPLA7 is a lysophosphatidylcholine hydrolase anchored on the endoplasmic reticulum which associates with LDs through its catalytic region (PNPLA7-C) in response to increased cyclic nucleotide levels. However, the interaction of PNPLA7 with LDs through its catalytic region is unknown. Herein, we demonstrate that PNPLA7-C localizes to the mature LDs ex vivo and also colocalizes with pre-existing LDs. Localization of PNPLA7-C with LDs induces LDs clustering via non-enzymatic intermolecular associations, while PNPLA7 alone does not induce LD clustering. Residues 742-1016 contains four putative transmembrane domains which act as a LD targeting motif and are required for the localization of PNPLA7-C to LDs. Furthermore, the N-terminal flanking region of the LD targeting motif, residues 681-741, contributes to the LD targeting, whereas the C-terminal flanking region (1169-1326) has an anti-LD targeting effect. Interestingly, the LD targeting motif does not exhibit lysophosphatidylcholine hydrolase activity even though it associates with LDs phospholipid membranes. These findings characterize the specific functional domains of PNPLA7 mediating subcellular positioning and interactions with LDs, as wells as providing critical insights into the structure of this evolutionarily conserved phospholipid-metabolizing enzyme family.

• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.31-35
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• 2008

Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by phospholipase $A_2$, has been considered responsible for the development of abnormal vascular reactivity during atherosclerosis. $Ca^{2+}$ influx was shown to be augmented in atherosclerotic artery which might be responsible for abnormal vascular reactivity. However, the mechanism underlying $Ca^{2+}$ influx change in atherosclerotic artery remains undetermined. The purpose of the present study was to examine the effects of LPC on L-type $Ca^{2+}$ current $(I_{Ca(L)})$ activity and to elucidate the mechanism of LPC-induced change of $I_{Ca(L)}$ in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased $I_{Ca(L)}$ through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of $I_{Ca(L)}$ was not significantly changed by LPC. Staurosporine (100 nM) or chelerythrine $(3{\mu}M)$, which is a potent inhibitor of PKC, significantly decreased basal $I_{Ca(L)}$, and LPC-induced increase of $I_{Ca(L)}$ was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal $I_{Ca(L)}$ significantly, and LPC-induced enhancement of $I_{Ca(L)}$ was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased $I_{Ca(L)}$ in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of $I_{Ca(L)}$ might be, at least in part, responsible for increased $Ca^{2+}$ influx in atherosclerotic artery.

• Molecules and Cells
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• 제43권12호
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• pp.989-1001
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• 2020

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen that causes salmonellosis and mortality worldwide. S. Typhimurium infects macrophages and survives within phagosomes by avoiding the phagosome-lysosome fusion system. Phagosomes sequentially acquire different Rab GTPases during maturation and eventually fuse with acidic lysosomes. Lysophosphatidylcholine (LPC) is a bioactive lipid that is associated with the generation of chemoattractants and reactive oxygen species (ROS). In our previous study, LPC controlled the intracellular growth of Mycobacterium tuberculosis by promoting phagosome maturation. In this study, to verify whether LPC enhances phagosome maturation and regulates the intracellular growth of S. Typhimurium, macrophages were infected with S. Typhimurium. LPC decreased the intracellular bacterial burden, but it did not induce cytotoxicity in S. Typhimurium-infected cells. In addition, combined administration of LPC and antibiotic significantly reduced the bacterial burden in the spleen and the liver. The ratios of the colocalization of intracellular S. Typhimurium with phagosome maturation markers, such as early endosome antigen 1 (EEA1) and lysosome-associated membrane protein 1 (LAMP-1), were significantly increased in LPC-treated cells. The expression level of cleaved cathepsin D was rapidly increased in LPC-treated cells during S. Typhimurium infection. Treatment with LPC enhanced ROS production, but it did not affect nitric oxide production in S. Typhimurium-infected cells. LPC also rapidly triggered the phosphorylation of IκBα during S. Typhimurium infection. These results suggest that LPC can improve phagosome maturation via ROS-induced activation of NF-κB pathway and thus may be developed as a therapeutic agent to control S. Typhimurium growth.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.199-199
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• 2005