TY - JOUR
T1 - Lysophosphatidylmethanol is a pan lysophosphatidic acid receptor agonist and is produced by autotaxin in blood
AU - Endo, Tomoko
AU - Kano, Kuniyuki
AU - Motoki, Rie
AU - Hama, Kotaro
AU - Okudaira, Shinichi
AU - Ishida, Mayuko
AU - Ogiso, Hideo
AU - Tanaka, Masayuki
AU - Matsuki, Norio
AU - Taguchi, Ryo
AU - Kanai, Motomu
AU - Shibasaki, Masakatsu
AU - Arai, Hiroyuki
AU - Aoki, Junken
N1 - Funding Information:
The Japan Science and Technology Agency (to J.A.); the Ministry of Education, Science and Culture (MEXT) of Japan (to J.A., M.S. and H.A.); the Target Protein Project of MEXT (to J.A.); ONO Science Foundation (to J.A.); and Takeda Science Foundation (to J.A.).
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Autotaxin
KW - Lysophosphatidic acid
KW - Lysophosphatidylcholine
KW - Lysophosphatidylmethanol
KW - Transphosphatidylation
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U2 - 10.1093/jb/mvp068
DO - 10.1093/jb/mvp068
M3 - Article
C2 - 19416959
AN - SCOPUS:68749121522
VL - 146
SP - 283
EP - 293
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 2
ER -