Article

Biological roles of lysophosphatidic acid signaling through its production by autotaxin.

Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Biochimie (impact factor: 3.02). 06/2010; 92(6):698-706. DOI:10.1016/j.biochi.2010.04.015 pp.698-706
Source: PubMed

ABSTRACT Lysophosphatidic acid (LPA) exhibits a wide variety of biological functions as a bio-active lysophospholipid through G-protein-coupled receptors specific to LPA. Currently at least six LPA receptors are identified, named LPA(1) to LPA(6), while the existence of other LPA receptors has been suggested. From studies on knockout mice and hereditary diseases of these LPA receptors, it is now clear that LPA is involved in various biological processes including brain development and embryo implantation, as well as patho-physiological conditions including neuropathic pain and pulmonary and renal fibrosis. Unlike sphingosine 1-phosphate, a structurally similar bio-active lysophospholipid to LPA and produced intracellularly, LPA is produced by multiple extracellular degradative routes. A plasma enzyme called autotaxin (ATX) is responsible for the most of LPA production in our bodies. ATX converts lysophospholipids such as lysophosphatidylcholine to LPA by its lysophospholipase D activity. Recent studies on ATX have revealed new aspects of LPA. In this review, we highlight recent advances in our understanding of LPA functions and several aspects of ATX, including its activity, expression, structure, biochemical properties, the mechanism by which it stimulates cell motility and its pahto-physiological function through LPA production.

0 0
 · 
0 Bookmarks
 · 
40 Views
  • Source
    Article: Lysoglycerophospholipids in chronic inflammatory disorders: The PLA(2)/LPC and ATX/LPA axes.
    Ioanna Sevastou, Eleanna Kaffe, Marios-Angelos Mouratis, Vassilis Aidinis
    [show abstract] [hide abstract]
    ABSTRACT: Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids, joining thromboxanes, leukotrienes and prostaglandins with which they share metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and LPA metabolism, such as the phospholipase A(2) superfamily (PLA(2)) and autotaxin (ATX, ENPP2), play central roles in regulating LPC and LPA levels and consequently their actions. LPC/LPA biosynthetic pathways will be briefly presented and LPC/LPA signaling properties and their possible functions in the regulation of the immune system and chronic inflammation will be reviewed. Furthermore, implications of exacerbated LPC and/or LPA signaling in the context of chronic inflammatory diseases, namely rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
    Biochimica et Biophysica Acta 07/2012; · 4.66 Impact Factor
  • Source
    Article: Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site.
    Andrés Nieto-Posadas, Giovanni Picazo-Juárez, Itzel Llorente, Andrés Jara-Oseguera, Sara Morales-Lázaro, Diana Escalante-Alcalde, León D Islas, Tamara Rosenbaum
    [show abstract] [hide abstract]
    ABSTRACT: Since 1992, there has been growing evidence that the bioactive phospholipid lysophosphatidic acid (LPA), whose amounts are increased upon tissue injury, activates primary nociceptors resulting in neuropathic pain. The TRPV1 ion channel is expressed in primary afferent nociceptors and is activated by physical and chemical stimuli. Here we show that in control mice LPA produces acute pain-like behaviors, which are substantially reduced in Trpv1-null animals. Our data also demonstrate that LPA activates TRPV1 through a unique mechanism that is independent of G protein-coupled receptors, contrary to what has been widely shown for other ion channels, by directly interacting with the C terminus of the channel. We conclude that TRPV1 is a direct molecular target of the pain-producing molecule LPA and that this constitutes, to our knowledge, the first example of LPA binding directly to an ion channel to acutely regulate its function.
    Nature Chemical Biology 11/2011; 8(1):78-85. · 14.69 Impact Factor
  • Source
    Article: Expression and regulation of Enpp2 in rat uterus during the estrous cycle.
    Hyo-Jin Ahn, Hyun Yang, Beum-Soo An, Kyung-Chul Choi, Eui-Bae Jeung
    [show abstract] [hide abstract]
    ABSTRACT: Ectonucleotide pyrophosphatase/phosphodiestrase 2 (Enpp2) isolated from the supernatant of human melanoma cells is a lysophospholipase D that transforms lysophosphatidylcholine into lysophospatidic acid. Although multiple analyses have investigated the function of Enpp2 in the hypothalamus, its role in the uterus during the estrous cycle is not well understood. In the present study, rat uterine Enpp2 was analyzed by RT-PCR, Western blotting, and immunohistochemistry. Quantitative PCR analysis demonstrated that uterine Enpp2 mRNA was decreased during estrus compared to proestrus and diestrus. To determine whether uterine Enpp2 expression is affected by sex steroid hormones, immature rats were treated with 17β-estradiol (E2), progesterone, or both on postnatal days 14 to 16. Interestingly, the expression of Enpp2 mRNA and protein were down-regulated by E2 in the uterus during estrus but not during proestrus or diestrus, suggesting that Enpp2 may play a role in uterine function during estrus. Enpp2 is primarily localized in the stromal cells of the endometrium during proestrus and estrus. During diestrus, Enpp2 was highly expressed in the epithelial cells of the endometrium. Taken together, these results suggest that uterine Enpp2 may be regulated by E2 and plays a role in reproductive functions during female rat development.
    Journal of veterinary science (Suwŏn-si, Korea) 12/2011; 12(4):379-85. · 0.89 Impact Factor

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

bio-active lysophospholipid
 
brain development
 
embryo implantation
 
G-protein-coupled receptors specific
 
hereditary diseases
 
knockout mice
 
LPA functions
 
LPA production
 
LPA receptors
 
lysophospholipase D activity
 
multiple extracellular degradative routes
 
neuropathic pain
 
new aspects
 
recent advances
 
Recent studies
 
renal fibrosis
 
six LPA receptors
 
structurally similar bio-active lysophospholipid
 
various biological processes
 
wide variety
 

Shinichi Okudaira