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Lysophosphatidic acid

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
Sheuli Afroz, Ayano Yagi, Kouki Fujikawa, M Motiur Rahman, Katsuya Morito, Tatsuya Fukuta, Shiro Watanabe, Emi Kiyokage, Kazunori Toida, Taro Shimizu, Tatsuhiro Ishida, Kentaro Kogure, Akira Tokumura, Tamotsu Tanaka
Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice...
February 17, 2018: Prostaglandins & Other Lipid Mediators
Deron R Herr, Jolin Hwee-Jing Ong, Wei-Yi Ong
Autotaxin is a dual-function ecto-enzyme, encoded by the gene ENPP2, which is the primary source of the bioactive signaling lipid, lysophosphatidic acid. Aberrations in autotaxin/lysophosphatidic acid signaling have been associated with a number of neurological, psychiatric, neoplastic, and neurodevelopmental conditions, such as pain, pruritus, glioblastoma multiforme, multiple sclerosis, Alzheimer's disease, hydrocephalus, and schizophrenia. This Viewpoint offers a brief overview of the likely indications for therapeutic targeting of autotaxin, in disorders affecting the nervous system...
February 19, 2018: ACS Chemical Neuroscience
Eun-Hye Hong, Ji-Ye Kim, Jeong-Hoon Kim, Dae-Sik Lim, Minkyu Kim, Jeong-Yoon Kim
Proper dendrite development is essential for establishing neural circuitry, and Rho GTPases play key regulatory roles in this process. From mouse brain lysates, we identified Brefeldin A-inhibited guanine exchange factor 2 (BIG2) as a novel Rho GTPase regulatory protein involved in dendrite growth and maintenance. BIG2 was highly expressed during early development, and knockdown of the ARFGEF2 gene encoding BIG2 significantly reduced total dendrite length and the number of branches. Expression of the constitutively active ADP-ribosylation factor 1 ARF1 Q71L rescued the defective dendrite morphogenesis of ARFGEF2-null neurons, indicating that BIG2 controls dendrite growth and maintenance by activating ARF1...
February 17, 2018: Molecular Neurobiology
Yoshinori Okamoto, Akira Aoki, Koji Ueda, Hideto Jinno
Estrogen is reported to be involved in mammary tumorigenesis. To unveil metabolic signatures for estrogen-induced mammary tumorigenesis, we carried out serum metabolomic analysis in an estrogen-induced mammary tumor model, female August Copenhagen-Irish/Segaloff (ACI/Seg) rats, using liquid chromatography-mass spectrometry. In contrast to the control group, all rats with an implanted 17β-estradiol (E2) pellet developed mammary tumors during this experiment. E2 treatment significantly suppressed body weight gain...
February 15, 2018: Toxicology Letters
Chen Xiaodan, Song Zijun, Chen Rui, Tan Shuyi, Huang Chunhuang, Liu Yanhui, Cheng Bin, Fu Qiang
Lysophosphatidic acid is a serum-derived growth factor that is involved in wound healing. Although in its infancy, a growing body of evidence has demonstrated that lysophosphatidic acid exerts a potentially significant role in regulating bone cell biology. However, previous studies mainly focused on the osteoinductive potential of lysophosphatidic acid, its effects on bone tissue vascularization, another essential element during bone regeneration, remains ill-defined so far. Here in this study, we examined the effects of lysophosphatidic acid on osteogenic differentiation as well as the angiogenesis-inducing capacity of pre-osteoblasts, a cell population that coordinates osteogenic and angiogenic processes in bone regenerating niche...
February 15, 2018: Connective Tissue Research
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
Takuya Ogawa, Asako Tanaka, Jun Kawamoto, Tatsuo Kurihara
1-Acyl-sn-glycerol-3-phosphate acyltransferase (designated as PlsC in bacteria) catalyzes the acylation of lysophosphatidic acid and is responsible for the de novo production of phosphatidic acid, a precursor for the synthesis of various membrane glycerophospholipids. Because PlsC is an integral membrane protein, it is generally difficult to solubilize it without causing its inactivation, which has been hampering its biochemical characterization despite its ubiquitous presence and physiological importance. Most biochemical studies of PlsC have been carried out by using crude membrane preparations or intact cells...
February 5, 2018: Journal of Biochemistry
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
Yiting Qiao, Tongyu Li, Shusen Zheng, Hangxiang Wang
The Hippo tumor suppressor pathway is critical for balancing cellular differentiation and proliferation in response to cell-cell contact, mechanical signals and diffusible signals such as lysophosphatidic acid. Hippo pathway signaling is frequently dysregulated in gastric cancer (GC), as well as many other kinds of solid tumors, contributing to multiple aspects of malignant progression including unchecked cell division and metastasis. Considering the importance of this Hippo pathway in cancer, its pharmacological disruption may be of huge benefit in the fight against this disease...
January 30, 2018: Cancer Letters
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
Megumi Honjo, Nozomi Igarashi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Kuniyuki Kano, Junken Aoki, Robert N Weinreb, Makoto Aihara
Purpose: To compare the levels of autotaxin (ATX), lysophosphatidic acid (LPA), and lysophosphatidylcholine (LPC) in the aqueous humor (AH) of healthy control subjects with those of patients with different subtypes of glaucoma, and also to investigate the relationship of the ATX-LPA pathway with IOP and subtype of glaucoma. Methods: This study included 164 eyes of 164 consecutive cases of cataract and glaucoma surgery (37 healthy, 31 normal tension glaucoma, 49 primary open angle glaucoma, 28 secondary open angle glaucoma, and 19 exfoliation glaucoma)...
February 1, 2018: Investigative Ophthalmology & Visual Science
Ji Hee Ha, Rangasudhagar Radhakrishnan, Muralidharan Jayaraman, Mingda Yan, Jeremy D Ward, Kar-Ming Fung, Katherine M Moxley, Anil K Sood, Ciro Isidoro, Priyabrata Mukherjee, Yong Sang Song, Danny N Dhanasekaran
Although hypoxia has been shown to reprogram cancer cells toward glycolytic shift, the identity of extrinsic stimuli that induce metabolic reprogramming independent of hypoxia, especially in ovarian cancer, is largely unknown. In this study, we use patient-derived ovarian cancer cells and high-grade serous ovarian cancer cell lines to demonstrate that lysophosphatidic acid (LPA), a lipid growth factor and GPCR ligand whose levels are substantially increased in ovarian cancer patients, triggers glycolytic shift in ovarian cancer cells...
January 31, 2018: Cancer Research
Iuliia Pavlyk, Nicolae A Leu, Pavan Vedula, Satoshi Kurosaka, Anna Kashina
β- actin plays key roles in cell migration. Our previous work demonstrated that β- actin in migratory non-muscle cells is N-terminally arginylated and that this arginylation is required for normal lamellipodia extension. Here we examined the function of β- actin arginylation in cell migration. We found that arginylated β- actin is concentrated at the leading edge of lamellipodia and that this enrichment is abolished after serum starvation as well as in contact-inhibited cells in confluent cultures, suggesting that arginylated β- actin at the cell leading edge is coupled to active migration...
January 31, 2018: Traffic
Yeongho Kim, Ee Leng Terng, Wayne R Riekhof, Edgar B Cahoon, Heriberto Cerutti
Understanding the unique features of triacylglycerol (TAG) metabolism in microalgae may be necessary to realize the full potential of these organisms for biofuel and biomaterial production. In the unicellular green alga Chlamydomonas reinhardtii a chloroplastic (prokaryotic) pathway has been proposed to play a major role in TAG precursor biosynthesis. However, as reported here, C. reinhardtii contains a chlorophyte-specific lysophosphatidic acid acyltransferase, CrLPAAT2, that localizes to endoplasmic reticulum (ER) membranes...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
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
Jesse Zhan, Jonathan Weng, Brian G Hunt, W Sean Davidson, Min Liu, Chunmin C Lo
Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are gastrointestinal peptides that play an important role in controlling energy homeostasis. Lymphatic ApoA-IV and plasma CCK secretion are mediated via a chylomicron formation-dependent pathway during a dietary lipid infusion. Given their similar roles as satiating proteins, the present study examines how the two peptides interact in their function. Specifically, this study sought to understand how ApoA-IV regulates CCK secretion. For this purpose, Cck gene expression in the small intestines of ApoA-IV knockout (ApoA-IV-KO) and wild-type (WT) mice were compared under an array of feeding conditions...
January 26, 2018: Physiology & Behavior
Ryan M Bradley, Robin E Duncan
PURPOSE OF REVIEW: Lysophosphatidic acid acyltransferases (LPAATs)/acylglycerophosphate acyltransferases (AGPATs) are a homologous group of enzymes that all catalyze the de novo formation of phosphatidic acid from lysophosphatidic acid (LPA) and a fatty acyl-CoA. This review seeks to resolve the apparent redundancy of LPAATs through examination of recent literature. RECENT FINDINGS: Recent molecular studies suggest that individual LPAAT homologues produce functionally distinct pools of phosphatidic acid, whereas gene ablation studies demonstrate unique roles despite a similar biochemical function...
January 25, 2018: Current Opinion in Lipidology
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
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