Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by K Hama
Total Records ( 2 ) for K Hama
  T Endo , K Kano , R Motoki , K Hama , S Okudaira , M Ishida , H Ogiso , M Tanaka , N Matsuki , R Taguchi , M Kanai , M Shibasaki , H Arai and J. Aoki
 

Lysophosphatidic acid (LPA) is a simple phospholipid but has numerous biological effects through a series of G-protein-coupled receptors specific to LPA. In general, LPA is short-lived when applied in vivo, which hinders most pharmacological experiments. In our continuing study to identify stable LPA analogues capable of in vivo applications, we identified here lysophosphatidylmethanol (LPM) as a stable and pan-LPA receptor agonist. A synthetic LPM activated all five LPA receptors (LPA1–5), and stimulates both cell proliferation and LPA-receptor-dependent cell motility. In addition, LPM showed a hypertensive effect in rodent when applied in vivo. We found that, when fetal calf serum was incubated in the presence of methanol, formation of LPM occurred rapidly, whereas it was completely blocked by depletion of autotaxin (ATX), a plasma enzyme that converts lysophosphatidylcholine (LPC) to LPA. When recombinant ATX was incubated with LPC in the presence of methanol, both LPM and LPA were produced with a ratio of 1:10, showing that ATX has transphosphatidylation activity in addition to its lysophospholipase D activity. Administration of methanol in mice resulted in the formation of several micromoles of LPM in plasma, which is much higher than that of LPA. The present study identified LPM as a novel and stable lysophospholipid mediator with LPA-like activities and ATX as a potential synthetic enzyme for LPM.

  K Nakanaga , K Hama and J. Aoki
 

Autotaxin (ATX) is an ecto-enzyme responsible for lysophosphatidic acid (LPA) production in blood. ATX is present in various biological fluids such as cerebrospinal and seminal fluids and accounts for bulk LPA production in these fluids. ATX is a member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family and was originally isolated from conditioned medium of melanoma cells as an autocrine motility stimulating factor. LPA, a second-generation lipid mediator, binds to its cognate G protein-coupled receptors through which it exerts a number of biological functions including influencing cell motility and proliferation stimulating activity. Some of the biological roles of LPA can be mediated by ATX. However, there are other LPA-producing pathways independent of ATX. The accumulating evidences for physiological and pathological functions of ATX strongly support that ATX is an important therapeutic target. This review summarizes the historical aspects, structural basis, pathophysiological functions identified in mice studies and clinical relevance discovered by measuring the blood ATX level in human. The general features and functions of each NPP family member will be also briefly reviewed. The presence of the ATX gene in other model organisms and recently developed ATX inhibitors, both of which will be definitely useful for further functional analysis of ATX, will also be mentioned.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility