• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.1-11
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• 2015

Lysophosphatidic acid (LPA) is a signaling lipid that binds to six known lysophosphatidic acid receptors (LPARs), named $LPA_1-LPA_6$. These receptors initiate signaling cascades relevant to development, maintenance, and healing processes throughout the body. The diversity and specificity of LPA signaling, especially in relation to cancer and autoimmune disorders, makes LPA receptor modulation an attractive target for drug development. Several LPAR-specific analogues and small molecules have been synthesized and are efficacious in attenuating pathology in disease models. To date, at least three compounds have passed phase I and phase II clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. This review focuses on the promising therapeutic directions emerging in LPA signaling toward ameliorating several diseases, including cancer, fibrosis, arthritis, hydrocephalus, and traumatic injury.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.109-110
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• 2003

Phospholipids function as major components of biological membranes as well as precursors of biologically active lipid messengers. It is well known that arachidonic acid attached at the sn-2 position of phosphoglycerides serves as a precursor of prostaglandins and leukotrienes. Recently, it has been recognized that lysophospholipids such as lysophosphatidic acid, sphingosine 1-phosphate, lysophosphatidylserine and monoglyceride also function as lipid messengers with a variety of biological activities. (omitted)

• Journal of Microbiology and Biotechnology
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• v.8 no.1
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• pp.81-88
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• 1998

The determination of appropriate parameters and parameter conditions is very important for the optimization of production of target materials. Taguchi's method has been used widely as the basis for development trials and optimization during industrial process design. Reaction variables which influence product yield are easily determined and their effects are revealed by just a few reactions, negating the need for extensive experimental investigation. There are usually some factors that are responsible for variations in process characteristics, so called noise factors. Controlling noise factors is very costly and difficult or impossible. Taguchi's experimental design method was examined to determine the control factor's level that is less sensitive to the changes in environmental conditions and other noise factors without control of noise factors. In this study, optimization of lipase-catalyzed production of lysophosphatidic acid (LPA) which has various physiological functions was performed by Taguchi's method. We obtained LPA yields ($66.5\%$) with low variance (5.32) at 400 RPM, molar ratio of 40 : 3 (mol) (fatty acid: G-3-P), 48 h, and $50^{\circ}C$. Thus, bioactive LPA with a desired fatty acid moiety could be produced with high yields and low variance despite various environmental noise factors.

• BMB Reports
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• v.39 no.5
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• pp.626-635
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• 2006

Lysophosphatidic acid acyltransferase (LPAAT) is an intrinsic membrane protein that catalyzes the synthesis of phosphatidic acid (PA) from lysophosphatidic acid (LPA). It is well known that LPAAT is involved in lipid biosynthesis, while its role in tumour progression has been of emerging interest in the last few years. To date, seven members of the LPAAT gene family have been found in human. Here we report a novel LPAAT member, designated as LPAAT-theta, which was 2728 base pairs in length and contained an open reading frame (ORF) encoding 434 amino acids. The LPAAT-theta gene consisted of 12 exons and 11 introns, and mapped to chromosome 4q21.23. LPAAT-theta was ubiquitously expressed in 18 human tissues by RT-PCR analysis. Subcellular localization of LPAAT-theta-EGFP fusion protein revealed that LPAAT-theta was distributed primarily in the endoplasmic reticulum (ER) of COS-7 cells. Furthermore, we found that the overexpression of LPAAT-theta can induce mTOR-dependent p70S6K phosphorylation on Thr389 and 4EBP1 phosphorylation on Ser65 in HEK293T cells.

• International Journal of Oral Biology
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• v.47 no.2
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• pp.25-31
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• 2022

Lysophosphatidic acid (LPA) is a bioactive lipid messenger involved in the pathogenesis of chronic inflammation and various diseases. Recent studies have shown an association between periodontitis and neuroinflammatory diseases such as Alzheimer's disease, stroke, and multiple sclerosis. However, the mechanistic relationship between periodontitis and neuroinflammatory diseases remains unclear. The current study found that lysophosphatidic acid receptors 1 (LPAR1) and 6 (LPAR6) exhibited increased expression in primary microglia and astrocytes. The primary astrocytes were then treated using medium conditioned to mimic periodontitis through addition of Porphyromonas gingivalis lipopolysaccharides, and an increased nitric oxide (NO) production was observed. Application of conditioned medium from human periodontal ligament stem cells with or without LPAR1 knockdown showed a decrease in the production of NO and expression of inducible nitric oxide synthase and interleukin 1 beta. These findings may contribute to our understanding of the mechanistic link between periodontitis and neuroinflammatory diseases.

• Biomedical Science Letters
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• v.15 no.4
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• pp.349-353
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• 2009

Lysophosphatidic Acid (LPA) is a bioactive lysophospholipid that is a potent signaling molecule able to provoke a variety of cellular responses in many cell types such as differentiation, inflammation and apoptosis. In this study, we have investigated the effect of LPA on Nitric oxide (NO)-induced apoptosis in rabbit articular chondrocytes. LPA dramatically reduced NO induced apoptosis of chondrocytes determined by phase contrast microscope and MTT assay. When chondrocytes alone treated with LPA, LPA induced phosphorylation of p70S6kinase, a serine/threonine kinase that acts downstream of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphoinositide-dependent kinase-1 (PDK-1) in the PI3 kinase pathway, dose-dependently detected by Western blot analysis. Phosphorylation of p70S6k with LPA was reduced expression of p53 in NO-induced apoptosis of chondrocytes. Also, inhibition of p70S6kinase with rapamycin was enhanced expression of p53 in chondrocytes. Our findings collectively suggest that LPA regulates NO induced apoptosis through p70S6kinase pathway in rabbit articular chondrocytes.

• Bulletin of the Korean Chemical Society
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• v.17 no.7
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• pp.575-577
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• 1996

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.96.1-96.1
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• 2003

Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types. However, we were surprised to find that LPA inhibits melanocyte proliferation. Thus, we further investigated the possible signaling pathways involved in melanocyte growth inhibition. We first examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were observed in concert with the inhibition of melanocyte proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA. (omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.101-101
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• 2004

• International Journal of Oral Biology
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• v.45 no.2
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• pp.42-50
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• 2020

Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.