By biochemical analysis, Tokumura et al. (2002) determined that lysoPLD has a substrate preference for lysophosphatidylcholine, with the production of physiologically active lysophosphatidic acid. Activity was enhanced in the presence of Co(2+) and inhibited by both ATP and a synthetic substrate for nucleotide. Serum lysoPLD activity increased in normal pregnant women at the third trimester and was increased further in patients threatened with preterm delivery.
NCBI Summary:
The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]
General function
Enzyme
Comment
Cellular localization
Secreted
Comment
Ovarian function
Luteinization
Comment
Preferable existence of polyunsaturated lysophosphatidic acids in human follicular fluid from patients programmed with in vitro fertilization. Yamamoto J et al. (2016) Lysophosphatidic acid (LPA) exerts diverse physiological effects on various types of animal cells, including reproductive cells, through its binding to six LPA receptors. We previously found that LPA promoted maturation of the nucleus and cytoplasm of mouse and hamster oocytes surrounded by cumulus cells in vitro. Using gas-liquid chromatography, we previously reported detection of several species of LPA by analyzing the fatty acid methyl esters derived from thin layer chromatography-purified LPA in lipid extract from incubated follicular fluids programmed with in vitro fertilization. In this study using liquid chromatography- tandem mass spectrometry, we directly detected high levels of linoleoyl, arachidonoyl, and docosahexaenoyl LPAs in human follicular fluid. This unique molecular species composition of LPA was suggested to be due to a balance between the low LPA-degrading activity and high LPA-producing activity of autotaxin in human follicular fluid. Our results suggest that polyunsaturated LPAs produced by autotaxin in human follicular fluid exert unknown physiological effects on cumulus cells.//////////////////
Autotaxin as a novel, tissue remodeling-related factor in regressing corpora lutea of cycling rats. Masuda K 2013 et al.
Autotaxin (ATX) generates lysophosphatidic acid (LPA) from glycerophospholipid through lysophospholipase D (lysoPLD) activity in cooperation with phospholipase A. We studied its expression and possible functional roles in the ovary of non-fertile cycling rats. Immunohistochemistry revealed that ATX was located predominantly in luteal steroidogenic cells of corpora lutea (CL) but not any follicles. ATX expression was modest in the newest generation and augmented in older generations of CL undergoing structural regression. ATX expression in the whole ovary and lysoPLD activity in circulating blood did not alter during the estrous cycle. Among LPA receptors LPA1-4 examined, LPA4 was densely present on migratory cells, probably phagocytes, at the degenerative foci within regressing CL. A bolus administration of anti-ATX antibody or LPA into ovarian bursa in vivo had little effects on apoptotic cell death of luteal cells, as evaluated with cleaved caspase-3 expression, but caused altered numbers in neutrophil and macrophage in regressing CL, as evaluated by immunological detection of each cell marker. Those treatments together with bromodeoxy uridine revealed the stimulatory effect of ATX/LPA pathway on fibroblasts proliferation in regressing CL. These results indicate that ATX is increasingly expressed by structurally regressing CL and play definite local actions on phagocytes recruitment and fibroblasts proliferation responsible for tissue remodeling. This article is protected by copyright. All rights reserved.
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Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells.
Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is induced in incubated human follicular fluid by lysophospholipase D. It is well known that LPA functions as a growth factor and the hypothesis that LPA in human follicular fluid takes a part in meiosis of oocytes is quite plausible. Hinokio K, et al studied the effects of LPA on the maturation of golden hamster immature oocytes in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation rates in the LPA and EGF groups were significantly higher than in the control group and the other growth factors did not show any stimulatory effect (LPA group; 74.3% (75/101), EGF group; 82.4% ;(9/108) vs. control group; 60.2% ;59/98, p < 0.05, p < 0.01, respectively). When the cells of cumulus were removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment EGF and LPA did not significantly enhance the stimulatory effect observed with LPA alone on maturation in vitro. The penetration rate determined by the zona-free hamster oocyte test was significantly higher in the LPA group than in the control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic maturation of hamster immature oocytes via cumulus cells.
Budnik LT, et al reported that Lysophosphatidic acid antagonizes the morphoregulatory effects of the luteinizing hormone on luteal cells: possible role of small Rho-G-proteins.
Lysophosphatidic acid (LPA) is a biologically active phospholipid recently introduced as a new marker for ovarian cancer. Because high concentrations of LPA have also been found in the follicular fluid from healthy subjects, one can presume that this biological mediator may have relevance for normal ovarian physiology as well. We have reported earlier that luteal cells possess specific binding sites for LPA. Using these cells as a model, we show now that LPA is able to modulate the morphological cell shape changes induced by LH in that it inhibits the formation of stellate processes induced by LH. This morphoregulatory effect of LPA is mimicked by cytotoxic necrotizing factor 1, a bacterial toxin known to activate small G-proteins from the Rho family. On the other hand, C3-exotransferase that acts mainly through the inhibition of Rho A mimics the effects of LH. Furthermore, we report here that the morphoregulatory effects of LPA are accompanied by the translocation of Rho proteins from the cytosol to cell membrane, an effect generally considered to be an indicator for the activation of Rho-GTPases. During the development and rescue of the corpus luteum, major morphoregulatory effects are exerted by LH that appear to be modulated by LPA via an activation of Rho proteins.