Disease relevance of LPA

• We demonstrate that in squamous cell carcinoma cells, stimulation with the GPCR agonists LPA or carbachol specifically results in metalloprotease cleavage and release of amphiregulin (AR) [1].
• Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10) [2].
• Lysophosphatidic acid (LPA; 1-acyl-2-hydroxy-sn-glycero-3-phosphate) is a lipid growth factor that stimulates the proliferation of ovarian cancer cells [3].
• The results emphasize the usefulness of antigen detection in the rapid diagnosis of Hib infections, demonstrate that LPA is more sensitive and specific than CIE, and can be conveniently performed by physicians [4].
• Furthermore, stimulation with LPA enhances the survival of prostate cancer cells via activation of the inducible transcription factor nuclear factor-kappaB [5].

Psychiatry related information on LPA

• PATIENTS AND METHOD: A total of 1260 TCSs and 20,207 men from the GenPop completed a questionnaire that assessed LPA, and depression and anxiety disorder on the Hospital Anxiety and Depression Scale (HADS) [6].
• The activity surveys and treadmill tests were used to categorize Ss into high (8.5 METs or greater, n = 27) and low (6.0 METs or less, n = 23) physical activity groups (HPA/LPA), and the gynecological surveys were used to distinguish Ss who were on estrogen therapy (n = 17) and those who had never been on estrogen therapy (n = 33) [7].
• Altered 1-oleoyl-lysophosphatidic acid (LPA, 100 muM)-stimulated calcium responses occur in B-lymphoblast cell lines from bipolar disorder patients, but the mechanism(s) involved is uncertain [8].
• One of the programs (SP/LPA) trained children in speech discrimination, letter-sound correspondence, and phonemic awareness [9].

High impact information on LPA

• E-cadherin did not regulate a constitutively active mutant RTK (Neu*) or the ligand-dependent activation of LPA receptors or muscarinic receptors, which are two classes of G protein-coupled receptors [10].
• We stimulated serum-starved Swiss 3T3 fibroblasts with LPA and compared the effects of C3 exoenzyme, a Rho inhibitor, with those of Y-27632, a ROCK inhibitor [11].
• Consistently, the amount of GTP-Rac increased significantly by Y-27632 in LPA-stimulated cells [11].
• Y-27632 treatment suppressed LPA-induced formation of stress fibers and focal adhesions as did C3 exoenzyme but induced membrane ruffles and focal complexes, which were absent in the C3 exoenzyme-treated cells [11].
• To better dissect the relationship between Gas2 phosphorylation and the modification of the microfilament architecture we used specific stimuli for both membrane ruffling (PDGF and PMA) and stress fiber formation (L-alpha-lysophosphatidic acid LPA) (Ridley, A. J., and A. Hall. 1992. Cell. 70:389-399) [12].

Chemical compound and disease context of LPA

• In fibroblasts from patients with Salla disease, a newly discovered lysosomal storage disorder, the lysosomes were brightly stained only with LPA, indicating the presence of increased amounts of sialic acid residues in the lysosomal inclusions [13].
• Importantly, the following lysophospholipid species are significantly increased in ascites from patients with ovarian cancer, compared to patients with nonmalignant diseases (e.g., liver failure): LPA (including acyl-, alkyl-, and alkenyl-LPA species), lysophosphatidylinositol, and sphingosylphosphorylcholine [14].
• Renal biopsy specimens from patients with membranous nephropathy were stained with rhodamine-labeled limulus polyphemus (LPA) and tricum vulgaris (WGA) [15].
• The lectin binding pattern of PAS-positive macrophages in Whipple's disease was examined with SBA, LPA, UEA I, PNA and WGA [16].

Biological context of LPA

• RhoA activation with LPA or transfection with V14RhoA reverted the inhibitory effect and induced stress fibers on FNIII7-10+FNIII4-5 [17].
• LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level [18].
• Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Qp) were calculated [19].
• Apolipoprotein E epsilon4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA [2].
• Insulin and 2-hour glucose levels are inversely related to Lp(a) concentrations controlled for LPA genotype [20].

Anatomical context of LPA

• Application of carbohydrate-specific lectins (ConA, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, SNA) on deparaffinated lung tissue sections from sepsis-associated fatalities and control cases results to some extent in different staining patterns of alveolar epithelial cells and subepithelial seromucous glands of the bronchi [21].
• LPA1 also traffics from cell membranes to the nucleus in response to LPA (lysophosphatidic acid) [22].
• Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air [19].
• Recombinant protein produced in COS 7 cells exhibited LPAAT activity with a preference for LPA as the acceptor phosphoglycerol and arachidonyl coenzyme A as the acyl donor [23].
• Although LPA potently enhances keratinocyte migration, it strongly induces growth arrest of proliferating epidermal cells [24].

Associations of LPA with chemical compounds

• About 80% of LPA receptors (N-acetylneuraminic acid) were removed from RBC surfaces by neuraminidase treatment [25].
• LPA is converted to phosphatidic acid, itself a lipid mediator, by an LPA acyltransferase (LPAAT) [23].
• The enzyme responsible for the generation of MAG, LPA phosphatase, has been identified in plants and purified by successive chromatography separations on octyl-Sepharose, Blue Sepharose, Superdex-75, and heparin-agarose to apparent homogeneity from developing peanuts [26].
• Sphingosine 1-phosphate, a putative messenger with some structural similarities to LPA, elicits a transient rise in intracellular [Ca2+] only at micromolar doses; however, cross-desensitization experiments indicate that sphingosine 1-phosphate does not act through the LPA receptor [27].
• Nine of these compounds induced platelet aggregation with the following order of potency: SPP < cAGP < DOXP-OH < (L)NAPS = (D)NAPS < (R)PNPA = (S)PNPA < LPA < AGP, EC50 varying between 9.8 nM and 8.3 microM [28].

Physical interactions of LPA

• The most impressing changes of LPA- and WGA-binding sites we observed during parturition in the extracellular matrix [29].

Enzymatic interactions of LPA

• Phospholipase D catalyzed hydrolysis of phospholipids generates phosphatidic acid (PA) which is subsequently metabolized to lyso-PA (LPA) or diacylglycerol (DAG) [30].

Regulatory relationships of LPA

• The results suggest that 100 muM LPA stimulates calcium entry through channels with characteristics similar to TRPC3, as TRPC6 and 7 are absent in B-lymphoblasts [8].
• Additionally, siRNA for LPA(1-3) receptors partially blocked LPA-induced IL-8 production and activation of MAPKs [31].
• LPA completely fails to induce chemotaxis in Smad3-deficient cells, whereas growth inhibition is at least in part reduced [24].
• LPA also induced phosphorylation of mitogen-activated protein kinase (p42(MAPK) and p44(MAPK)) in HOFNH30-transfected but not vector-transfected RBL-2H3 cells [32].
• CPA inhibited LPA-induced prolactin release but not hyposmotically-induced release [33].

Other interactions of LPA

• The G protein-coupled family of receptors, including LPA, also is an attractive target to drugs, although their frequent pleiotropic functions may be at times toxic and lack specificity [34].
• The metabolism of long-chain fatty acids in brain and their incorporation into signaling molecules such as diacylglycerol and LPA and into structural components of membranes, including myelin, requires activation by long-chain acyl-CoA synthetase (ACSL) [35].
• The high values of APOE*E4 and LPA PNR*7 together with the intermediate linkage disequilibrium values between APOE and APOC1 alleles in comparison with Europeans and Africans suggest a certain degree of Sub-Saharan influence in the current Moroccan population [36].
• PA generated by agonist- or reactive oxygen species (ROS)-mediated activation of the PLDI and PLD2 isoforms can be subsequently converted to lysoPA (LPA) or diacylglycerol (DAG) by phospholipase A1/A2 or lipid phosphate phosphatases [37].
• These findings indicate an essential role of Smad3 in diverse biological properties of LPA-stimulated keratinocytes [24].

Analytical, diagnostic and therapeutic context of LPA

• In these cells, formation of stress fibres induced by LPA stimulation, or microinjection of activated Rho; (V14Rho), was inhibited [38].
• Solutions containing 2% w/w of LPA made by emulsion polymerization were simple to prepare, resulting in excellent performance as a replaceable matrix for DNA sequencing by capillary electrophoresis [39].
• With the use of a 0.5-T open magnet, a magnetic resonance-compatible exercise cycle, and cine phase-contrast techniques, time-dependent blood flow velocities were measured in the right (RPA), left (LPA), and main (MPA) pulmonary arteries and superior (SVC) and inferior (IVC) vena cavae of 10 healthy 10- to 14-yr-old subjects [40].
• LPA transgenic mice on a normal diet could be a useful animal model for the study of spontaneous human atherosclerosis, its treatment and prevention [41].
• Sequence analysis data from the cloned K IV-type 2 repeats revealed a high degree of LPA sequence conservation in exons as well as in introns both within and between the two libraries [42].

References