Physiological and pathophysiological roles of lysophosphatidic acids produced by secretory lysophospholipase D in body fluids.
Recently, a family of phospholipid mediators has received much attention because of its variety of biological activities. Lysophosphatidic acid (LPA) is a central member of the phospholipid autacoid family that exerts diverse effects through binding to and activation of several specific receptors coupled to G-proteins. In accordance with its function as a receptor agonist, there are pathways for extracellular generation of LPA in vivo. One pathway involves a novel lysophospholipase D activity that was originally found in rat plasma. LPA is also produced in significant amounts after incubation of various plasma-derived body fluids such as human follicular fluid at 25-37 degrees C. In animal models, LPA was shown to stimulate oocyte maturation, embryonic development and transport in the oviduct. An increase in serum lysophospholipase D activity was observed during pregnancy in human. These results suggest that LPA generated by lysophospholipase D is likely to play an important role in reproductive biology. LPA produced by lysophospholipase D activity in body fluids has also been observed under pathophysiological conditions: serum and ascitic fluid from ovarian cancer patients and serum from hypercholesterolemic rabbits. Hence, excess generation of LPA by lysophospholipase D activity in body fluids has been suggested to be relevant to the pathogenesis of cancer and atherosclerosis.
Tokumura
Akira
A
Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78 Shomachi, Tokushima, Japan. tokumura@ph.tokushima-u.ac.jp
D000818:Animals; D001794:Blood Pressure; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000378:metabolism*; D000099189:Lysophospholipase D
D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D