Enhancement of Lysophosphatidic Acid-Induced ERK Phosphorylation by Phospholipase D1 via the Formation of Phosphatidic Acid

2001 ◽  
Vol 281 (5) ◽  
pp. 1337-1342 ◽  
Author(s):  
Jang-Hee Hong ◽  
Seo-Ok Oh ◽  
Michael Lee ◽  
Young-Rae Kim ◽  
Dong-Uk Kim ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Erk Phosphorylation ◽  
Phospholipase D1

Growth factor-like phospholipids generated after corneal injury

1998 ◽  
Vol 274 (4) ◽  
pp. C1065-C1074 ◽  
Author(s):  
Károly Liliom ◽  
Zhiwei Guan ◽  
Jih-Lie Tseng ◽  
Dominic M. Desiderio ◽  
Gábor Tigyi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Growth Factor ◽  
Phosphatidic Acid ◽  
Aqueous Humor ◽  
Lysophosphatidic Acid ◽  
Xenopus Oocyte ◽  
Two Dimensional ◽  
Corneal Injury ◽  
Rabbit Eye ◽  
Cellular Regeneration

The present study provides evidence that growth factor-like glycerophosphate mediators of the lysophosphatidic acid (LPA) family are present in the aqueous humor and the lacrimal gland fluid of the rabbit eye. By use of a combination of HPLC, two-dimensional TLC, mass spectrometry, and the Xenopus oocyte bioassay, the LPA-like phospholipids LPA, cyclic PA, alkenyl-glycerophosphate (GP), lysophosphatidylserine, and phosphatidic acid were detected as physiological constituents of the fluids bathing the cornea. Corneal injury resulted in an increased production of some of these mediators. Alkenyl-GP, a novel member of the LPA family, has been identified in postinjury aqueous humor, establishing that it is generated endogenously. LPA and its homologues were found to be mitogenic in freshly dissociated keratocytes from uninjured corneas. There appears to be a link between the occurrence of LPA responsiveness in keratocytes activated by injury and the increase in LPA-like activity in aqueous humor. These data suggest that LPA and its homologues are involved in maintaining the integrity of the normal cornea and in promoting cellular regeneration of the injured cornea.

2- O -Carba-oleoyl cyclic phosphatidic acid induces glial proliferation through the activation of lysophosphatidic acid receptor

2018 ◽  
Vol 1681 ◽  
pp. 44-51 ◽  
Author(s):  
Shingo Nakajima ◽  
Mari Gotoh ◽  
Keiko Fukasawa ◽  
Hiromu Murofushi ◽  
Kimiko Murakami-Murofushi
Keyword(s):  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Glial Proliferation ◽  
Cyclic Phosphatidic Acid

Increased phosphatidic acid and decreased lysophosphatidic acid in response to thrombin is associated with inhibition of platelet aggregation

1993 ◽  
Vol 71 (9-10) ◽  
pp. 432-439 ◽  
Author(s):  
Jon M. Gerrard ◽  
Pauline Robinson ◽  
Michael Narvey ◽  
Archibald McNicol
Keyword(s):  
Platelet Aggregation ◽  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Human Platelet ◽  
Inhibitory Effect ◽  
Phospholipase A ◽  
Direct Role ◽  
Inhibition Of Platelet Aggregation ◽  
Phosphatidate Phosphohydrolase ◽  
Rule Out

Thromboxane A2, produced from the arachidonic acid released from platelet phospholipids by phospholipase A2, stimulates platelet aggregation. It remains unresolved whether additional products of platelet phospholipase A2 might promote aggregation. To address this question, we have used aspirin-treated platelets to block thromboxane A2 formation and studied the influence of the phospholipase A2 inhibitor U10029A on platelet aggregation and secretion in response to thrombin. U10029A at 100 μM markedly inhibited platelet aggregation, but had no effect on platelet secretion. Since this concentration of U10029A effectively blocked lysophosphatidic acid (LPA) formation, LPA was added and found to substantially reverse the inhibitory effect of U10029A in these platelets. Furthermore, the action of U10029A was not due to inhibition of phosphatidate phosphohydrolase because U10029A, unlike propranolol, did not inhibit this enzyme. Although it is not possible to conclusively rule out an effect of U10029A in addition to its inhibition of phospholipase A2, our results reveal that a product of phospholipase A2 other than thromboxane A2 is important for platelet aggregation, but not for secretion in response to thrombin. Our data suggest that this product is LPA. Since the amount of phosphatidic acid (PA) increased dramatically concurrent with inhibition of platelet aggregation, it is safe to conclude that PA has no direct role to promote platelet aggregation in response to thrombin.Key words: lysophosphatidic acid, phosphatidic acid, phospholipase A2, human platelet.

Phospholipase D1 and Potential Targets of Its Hydrolysis Product, Phosphatidic Acid

ChemInform ◽  
2003 ◽  
Vol 34 (28) ◽  
Author(s):  
N. T. Ktistakis ◽  
C. Delon ◽  
M. Manifava ◽  
E. Wood ◽  
I. Ganley ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Hydrolysis Product ◽  
Phospholipase D1

scholarly journals Characterization of dolichol and dolichyl phosphate phosphatase from soya beans (Glycine max)

1983 ◽  
Vol 213 (2) ◽  
pp. 513-518 ◽  
Author(s):  
K Ravi ◽  
J W Rip ◽  
K K Carroll
Keyword(s):  
Enzyme Activity ◽  
Glycine Max ◽  
Phosphatidic Acid ◽  
Phosphatase Activity ◽  
Lysophosphatidic Acid ◽  
Competitive Inhibition ◽  
High Yield ◽  
Dolichyl Phosphate ◽  
Ability To Act ◽  
Phosphorylated Compounds

A series of polyprenols, ranging in length from 15 to 22 isoprene units, has been isolated from soya beans (Glycine max) and purified by high-pressure liquid chromatography. N.m.r., i.r. and mass spectra of the compounds indicated that they are alpha-saturated polyprenols of the dolichol type. The amount present in dry seeds was about 9 mg/100 g, whereas dolichyl phosphate (Dol-P) was present only in trace amounts. Dol-P phosphatase activity was detected in the microsomal fraction of 5-day-old germinating soya-bean cotyledons. The Dol-P phosphatase activity was linear with respect to time and protein concentration and exhibited a broad pH optimum (pH 7-9). Triton X-100 was necessary for significant enzyme activity. Enzyme activity was slightly enhanced by EDTA, whereas dithiothreitol was without effect. An apparent Km of 5 microM was determined for Dol-P. Bivalent metal ions were not required for enzyme activity. A number of phosphorylated compounds tested as enzyme substrates (including a number of nucleoside phosphates, glucose 6-phosphate, sodium β 1 leads to 4Glc. Because of the ease of purification of the enzyme and high yield in the absence of contaminating glycosidases and proteinases, Bacteroides fragilis is a valuable source of endo-beta-galactosidase for the structural analysis of carbohydrate chains. -glycerophosphate and Na4P2O7) did not compete with [1-3H]Dol-P as substrate. A number of phospholipids were also tested for their ability to act as Dol-P phosphatase substrates. At 1 mM concentration, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid and lysophosphatidic acid each inhibited enzymic activity. However, at 0.1 mM concentration, phosphatidylcholine and phosphatidylethanolamine were slightly stimulatory, whereas phosphatidic acid and lysophosphatidic acid were still inhibitory. Phosphatidic acid showed competitive inhibition.

scholarly journals Purification and characterization of N-ethylmaleimide-insensitive phosphatidic acid phosphohydrolase (PAP2) from rat liver

1995 ◽  
Vol 308 (3) ◽  
pp. 983-989 ◽  
Author(s):  
I N Fleming ◽  
S J Yeaman
Keyword(s):  
Phosphatidic Acid ◽  
Rat Liver ◽  
Lysophosphatidic Acid ◽  
Gel Filtration ◽  
Purification And Characterization ◽  
Sds Page ◽  
Chromatography Columns ◽  
Triton X ◽  
Second Peak

N-Ethylmaleimide-insensitive phosphatidic acid phosphohydrolase (PAP; EC 3.1.3.4) was purified 5900-fold from rat liver. The enzyme was solubilized from membranes with octylglucoside, fractionated with (NH4)2SO4, and purified in the presence of Triton X-100 by chromatography on Sephacryl S300, hydroxyapatite, heparin-Sepharose and Affi-Gel Blue. Silver-stained SDS/PAGE indicated that the enzyme was an 83 kDa polypeptide. Sephacryl S-300 gel filtration also produced a second peak of enzyme activity, which was eluted from all of the chromatography columns at a different position from the purified enzyme. SDS/PAGE indicated that it contained three polypeptides (83 kDa, 54 kDa and 34 kDa), and gel filtration suggested that it was not an aggregate of the purified enzyme. Both forms were sensitive to inhibition by amphiphilic amines, Mn2+ and Zn2+, but not by N-ethylmaleimide. Purified PAP required detergent for activity, but was not activated by Mg2+, fatty acids or phospholipids. The enzyme was able to dephosphorylate lysophosphatidic acid or phosphatidic acid, and was inhibited by diacylglycerol and monoacylglycerol. No evidence was obtained for regulation of PAP by reversible phosphorylation.

The acylation of 1-acyl-sn-glycero-3-phosphate by neuronal nuclei and microsomal fractions of immature rabbit cerebral cortex

1990 ◽  
Vol 68 (3) ◽  
pp. 641-647 ◽  
Author(s):  
R. Roy Baker ◽  
H.-Y. Chang
Keyword(s):  
Cerebral Cortex ◽  
Phosphatidic Acid ◽  
Lysophosphatidic Acid ◽  
Monounsaturated Fatty Acids ◽  
Acid Formation ◽  
Nuclear Fraction ◽  
Neuronal Nucleus ◽  
Neuronal Nuclei ◽  
Low Concentrations ◽  
Rabbit Cerebral Cortex

The acylation of 1-acyl-sn-glycero-3-phosphate to form phosphatidic acid was studied using a neuronal nuclear fraction N1 and microsomal fractions P3, R (rough), S (smooth), and P (neuronal microsomes from nerve cell bodies) isolated from cerebral cortices of 15-day-old rabbits. The assays contained this lysophospholipid, ATP, CoA, MgCl2, NaF, dithiothreitol, and radioactive palmitate, oleate, or arachidonate. Of the subfractions, N1 and R had the highest specific activities (expressed per micromole phospholipid in the fraction). The rates with oleate were two to four times the values seen for phosphatidic acid formation from sn-[3H]glycero-3-phosphate and oleoyl-CoA. Using oleate or palmitate, fraction R had superior specific rates to N1 at low lysophosphatidic acid concentrations. With increasing lysophospholipid concentrations the specific rates of N1 and R came closer together and maintained at least a twofold superiority over fraction P. Fraction S had the lowest specific rates of phosphatidic acid formation. Fractions N1, R, and P showed a preference for palmitate and oleate over arachidonate, particularly at low concentrations of lysophosphatidic acid. For N1 and R, the preference was also more marked at higher concentrations of fatty acid. Thus a selectivity for saturated and monounsaturated fatty acids was shown in the formation of phosphatidic acid, as was a concentration of acylating activity in the neuronal nucleus and the rough endoplasmic reticulum.Key words: 1-acyl-sn-glycero-3-phosphate, acylation, neuronal nuclei, microsomes, cerebral cortex.

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