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LPA receptor

Seon-Ung Hwang, Kyu-Jun Kim, Eunhye Kim, Junchul David Yoon, Kyu Mi Park, Minghui Jin, Yongquan Han, Mirae Kim, Gabsang Lee, Sang-Hwan Hyun
Lysophosphatidic acid (LPA) is a phospholipid-derived signaling molecule with biological activities, such as stimulating cell proliferation, differentiation and migration. In the present study, we examined the effect of LPA on porcine oocytes during in vitro maturation (IVM) and subsequent embryonic development following parthenogenetic activation (PA) and in vitro fertilization (IVF). During IVM, the maturation medium was supplemented with various concentrations of LPA (0, 10, 30, and 60 μM). After 42 h of IVM, the 30 μM LPA-treated group showed a significant (P <0...
March 2, 2018: Theriogenology
Yu-Ting Bai, Rong Chang, Hua Wang, Feng-Jun Xiao, Ri-Li Ge, Li-Sheng Wang
Ferroptosis is an iron- and oxidative-dependent form of regulated cell death and may play important roles in maintaining myocardium homeostasis and pathology of cardiovascular diseases. Currently, the regulatory roles of lipid signals in regulating cardiomyocytes ferroptosis has not been explored. In this study, we show that ENPP2, as a lipid kinase involved in lipid metabolism, protects against erastin-induced ferroptosis in cardiomyocytes. The classical ferroptosis inducer erastin remarkably inhibits the growth which could be rescued by the small molecule Fer-1 in H9c2 cells...
March 15, 2018: Biochemical and Biophysical Research Communications
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Danyun Wang, Ning Yan, Xudong Yang, Yuan Ge, Dedong Xu, Guangyuan Shao, Zhongmin Peng
Objective: To investigate the correlation between epidermal growth factor receptor (EGFR) mutation and the histologic subtypes features or computed tomography (CT) findings in patients with resected pulmonary adenocarcinoma. Materials and Methods: We retrospectively reviewed 153 patients underwent surgical resected pulmonary adenocarcinoma. EGFR mutations were detected using the amplification refractory mutation system. Histologic subtype was classified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society pulmonary adenocarcinoma classification...
January 2018: Journal of Cancer Research and Therapeutics
David Ladrón de Guevara-Miranda, Román Darío Moreno-Fernández, Sara Gil-Rodríguez, Cristina Rosell-Valle, Guillermo Estivill-Torrús, Antonia Serrano, Francisco J Pavón, Fernando Rodríguez de Fonseca, Luis J Santín, Estela Castilla-Ortega
Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction...
February 26, 2018: Addiction Biology
Xueqian Wang, Haitao Hou, Kaida Song, Zhiqiang Zhang, Shuqiang Zhang, Ying Cao, Liming Chen, Qing Sang, Fang Lin, Hui Xu
LPA signaling plays important roles during cell migration and proliferation in normal and pathological conditions. However, its role during sensory organ development remains unknown. Here we show a LPA receptor Lpar2b is expressed in the posterior lateral line primordium (pLLP) and mechanosensory organs called neuromasts (NMs) in zebrafish embryos. Lpar2b loss-of-function significantly reduces the number of NMs and hair cells in the posterior lateral line (pLL). Further analysis reveals that Lpar2b regulates the patterning and tissue size of the pLLP...
2018: Frontiers in Molecular Neuroscience
Tangjun Zhou, Lin Du, Chen Chen, Chen Han, Xunlin Li, An Qin, Changqing Zhao, Kai Zhang, Jie Zhao
BACKGROUND/AIMS: Hypertrophic ligamentum flavum (LF) is a major cause of lumbar spinal stenosis. Our previous work showed that high levels of lysophosphatidic acid (LPA) expression are positively correlated with LF hypertrophy. This study aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied LPAR1 expression in human LF cells using PCR and western blotting. Cell viability cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1 knockdown or overexpression LF cells...
February 16, 2018: Cellular Physiology and Biochemistry
Caojian Zuo, Xiaodong Li, Jun Huang, Dongrui Chen, Kaida Ji, Yan Yang, Tingyan Xu, Ding-Liang Zhu, Chen Yan, Pingjin Gao
Aims: Cardiac myofibroblasts (CMFs) play a crucial role in the progression of pathological fibrotic cardiac remodeling. The expression of osteoglycin (OGN) is increased in diseased hearts; however, the role of OGN in pathological cardiac remodeling is not understood. Here we sought to determine the effect of OGN on cardiac interstitial fibrosis and investigated the molecular mechanisms of OGN in CMF activation and matrix production. Methods and results: We found that OGN expression was significantly upregulated in mouse hearts in response to chronic 14-day angiotensin II (Ang II) infusion...
February 5, 2018: Cardiovascular Research
Mayumi Hidaka, Mai Nishihara, Akira Tokumura
AIM: The intestinal mucus layer helps maintain intestinal homeostasis. In this study, we investigated the effects of lysophosphatidic acids (LPA) on differentiation of human colon carcinoma cell line, HT-29, to goblet cells with and without sodium butyrate, a known differentiation factor for intestinal cells. MAIN METHODS: Number and average size of cells with goblet-like morphology in five photographs per dish were measured for assessment of differentiation of HT-29 cells to goblet cells as well as their relative portion of surface of to whole surface area of the photograph...
February 2, 2018: Life Sciences
Ryoko Tsukahara, Shinji Yamamoto, Keisuke Yoshikawa, Mari Gotoh, Tamotsu Tsukahara, Hiroyuki Neyama, Satoshi Ishii, Noriyuki Akahoshi, Keisuke Yanagida, Hayakazu Sumida, Masatake Araki, Kimi Araki, Ken-Ichi Yamamura, Kimiko Murakami-Murofushi, Hiroshi Ueda
Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 receptor expression in corpus callosum elevated after the initiation of demyelination, and the hyperalgesia through Aδ-fibers following cuprizone-induced demyelination was mediated by LPA5 signaling...
February 2, 2018: Journal of Pharmacological Sciences
Junko Okabe-Kado, Yuki Hagiwara-Watanabe, Nozomi Niitsu, Takashi Kasukabe, Yasuhiko Kaneko
The NM23 gene is overexpressed in many hematological malignancies and its overexpression predicts poor treatment outcomes. NM23 overexpression is thought to suppress myeloid differentiation of leukemia cells, but the molecular mechanism is unknown. In breast cancer cells, the lysophosphatidic acid (LPA) receptor EDG2/lpa1 was downregulated by NM23-H1 overexpression, and this reciprocal expression pattern was associated with suppressed or induced cell motility/metastasis. Here, we examined the relationship between EDG2 and NM23 expression during myeloid differentiation of leukemia cells...
January 3, 2018: Leukemia Research
Megan Stevens, Christopher R Neal, Andrew H J Salmon, David O Bates, Steven J Harper, Sebastian Oltean
BACKGROUND/AIMS: Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). METHODS: The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b)...
January 26, 2018: Nephron
Laura Sánchez-Marín, David Ladrón de Guevara-Miranda, Mari Carmen Mañas-Padilla, Francisco Alén, Román D Moreno-Fernández, Caridad Díaz-Navarro, José Pérez-Del Palacio, María García-Fernández, Carmen Pedraza, Francisco J Pavón, Fernando Rodríguez de Fonseca, Luis J Santín, Antonia Serrano, Estela Castilla-Ortega
The systemic administration of lysophosphatidic acid (LPA) LPA1/3 receptor antagonists is a promising clinical tool for cancer, sclerosis and fibrosis-related diseases. Since LPA1 receptor-null mice engage in increased ethanol consumption, we evaluated the effects of systemic administration of an LPA1/3 receptor antagonist (intraperitoneal ki16425, 20 mg/kg) on ethanol-related behaviors as well as on brain and plasma correlates. Acute administration of ki16425 reduced motivation for ethanol but not for saccharine in ethanol self-administering Wistar rats...
January 26, 2018: Neuropharmacology
Kaede Takahashi, Kaori Fukushima, Shiho Otagaki, Kaichi Ishimoto, Kanako Minami, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits a variety of cellular responses via the activation of G protein-coupled transmembrane LPA receptors (LPA receptor-1 (LPA1) to LPA6). The aim of our study was to investigate effects of LPA receptors on soft agar colony formation in colon cancer cells treated with anticancer drugs. DLD1 cells were treated with fluorouracil (5-FU) or cisplatin (CDDP) for at least six months (DLD-5FU and DLD-CDDP cells, respectively). LPAR1 gene expression was markedly elevated in DLD-5FU cells...
February 2018: Journal of Receptor and Signal Transduction Research
LeAnn C Rogers, Ryan R Davis, Naveen Said, Thomas Hollis, Larry W Daniel
The paradoxical role of reactive oxygen species in cell death versus cell survival establishes a delicate balance between chemotherapy efficacy and management of detrimental side effects. Normal proliferative signaling requires that cells remain inside a redox range that allows reversible protein oxidation to occur. Shifting the redox environment toward highly reducing or oxidizing states leads to cellular stress and cell death. Reactive oxygen species produced in response to Taxol and cisplatin treatment are necessary for effective cancer cell killing but the same ROS leads to damaging side effects in normal tissues...
January 4, 2018: Redox Biology
Jeongrak Park, Jin-Hyuck Jang, Seojin Oh, Minhye Kim, Changhoon Shin, Minseok Jeong, Kyun Heo, Jong Bae Park, Sang Ryong Kim, Yong-Seok Oh
Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian cancer. This phospholipid elicits a wide range of cancer cell responses, such as proliferation, trans-differentiation, migration, and invasion, via various G-protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling pathway via which LPA induces migration of ovarian cancer cells. LPA induced robust phosphorylation of ezrin/radixin/moesin (ERM) proteins, which are membrane-cytoskeleton linkers, in the ovarian cancer cell line OVCAR-3...
January 9, 2018: Cellular Signalling
Guo Zhang, Yuan Cheng, Qi Zhang, Xiaoping Li, Jingwei Zhou, Jianliu Wang, Lihui Wei
Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX is a crucial factor that facilitates cancer progression; however, the effect of ATX on endometrial cancer has not been explored. The aim of the present study was to investigate the role of ATX in the progression of endometrial cancer. The immunohistochemical results revealed higher protein expression levels of ATX and LPA receptors (LPA 1, 2 and 3) in human endometrial cancer tissue than in non‑carcinoma tissue...
January 8, 2018: Molecular Medicine Reports
Yuriy V Loskutov, Caryn L Griffin, Kristina M Marinak, Andrey Bobko, Naira V Margaryan, Werner J Geldenhuys, Jann N Sarkaria, Elena N Pugacheva
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner...
January 11, 2018: Oncogene
Kaori Fukushima, Kaede Takahashi, Aya Kurokawa, Kaichi Ishimoto, Shiho Otagaki, Kanako Minami, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) signaling through six subtypes of LPA receptors (LPA1 to LPA6) regulates a variety of biological responses in cancer cells. The aim of our study was to evaluate an involvement of LPA receptors in the activation of cell motility by phorbol ester and anticancer drug treatments in melanoma A375 cells. Cells were treated with 12-O-tetradecanoylphorbol- 13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu) for 3 days. The cell motile activity of TPA treated cells was significantly higher than that of PDBu treated cells, correlating with LPAR5 expression levels...
January 5, 2018: Biochemical and Biophysical Research Communications
Megumi Honjo, Nozomi Igarashi, Junko Nishida, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Kuniyuki Kano, Junken Aoki, Makoto Aihara
Purpose: Dexamethasone (Dex) regulates aqueous humor outflow by inducing reorganization of the cytoskeleton and extracellular matrix (ECM) production. Rho kinase (ROCK) has an important role in this process, but the upstream pathway leading to its activation remains elusive. The purpose of the study was to determine the role of autotaxin (ATX), an enzyme involved in the generation of lysophosphatidic acid (LPA), in the Dex-induced fibrotic response and ECM production in human trabecular meshwork (HTM) cells...
January 1, 2018: Investigative Ophthalmology & Visual Science
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