Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroparsins were originally identified in locust corpus cardiacum extracts as folliculostatic or 'antigonadotropic' neuropeptides. This paper presents the cloning of two different neuroparsin precursor cDNAs from the brain of the desert locust, Schistocerca gregaria. The first transcript encodes the precursor (Scg-NPP1) of S. gregaria neuroparsin A and B, whereas the second codes for a novel neuroparsin-related peptide precursor (Scg-NPP2). Both precursors display significant sequence similarities with each other and with the Locusta migratoria neuroparsin (Lom-NPP) and Aedes aegypti ovary ecdysteroidogenic hormone (Aea-OEH1) precursors. Northern blot analysis revealed that these neuroparsin transcripts are present in larval and adult locust brains. Interestingly, the Scg-NPP2 mRNA content proved to be strongly regulated during the reproductive cycle in both adult males and females.
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PMID:cDNA cloning and transcript distribution of two different neuroparsin precursors in the desert locust, Schistocerca gregaria. 1142 14

The ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) multigene family contains five members. NPP1-3 are type II transmembrane metalloenzymes characterized by a similar modular structure composed of a short intracellular domain, a single transmembrane domain and an extracellular domain containing a conserved catalytic site. The short intracellular domain of NPP1 has a basolateral membrane-targeting signal while NPP3 is targeted to the apical surface of polarized cells. NPP4-5 detected by database searches have a predicted type I membrane orientation but have not yet been functionally characterized. E-NPPs have been detected in almost all tissues often confined to specific substructures or cell types. In some cell types, NPP1 expression is constitutive or can be induced by TGF-beta and glucocorticoids, but the signal transduction pathways that control expression are poorly documented. NPP1-3 have a broad substrate specificity which may reflect their role in a host of physiological and biochemical processes including bone mineralization, calcification of ligaments and joint capsules, modulation of purinergic receptor signalling, nucleotide recycling, and cell motility. Abnormal NPP expression is involved in pathological mineralization, crystal depositions in joints, invasion and metastasis of cancer cells, and type 2 diabetes. In this review we summarize the present knowledge on the structure and the physiological and biochemical functions of E-NPP and their contribution to the pathogenesis of diseases.
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PMID:Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. 1275 29

Ecto-nucleotide pyrophosphatase/phospho-diesterase-I enzyme (E-NPP), one of the type II transmembrane proteins, cleaves phosphodiester and phosphosulfate bonds of a variety of substrates including deoxynucleotides, NAD, and nucleotide sugars. Mammalian E-NPP consists of three closely related family proteins; E-NPP1 (PC-1), E-NPP2 (PDNP2/PD-Ialpha/autotaxin), and E-NPP3 (CD203c/PDNP3/PD-Ibeta/B10/gp130RB13-6) that express in different cells or at different locations even in the same cell. E-NPP3 is associated with malignant subversion and invasive properties. In this study, the expression and localization of E-NPP3 were investigated in human colon carcinoma. Western blotting showed strong E-NPP3 expression in cancer tissues and in the serum of colon carcinoma patients. Immunohistochemically, E-NPP3 was expressed not only in the apical but also in the basolateral plasma membranes of cancer cells. No prominent pattern of intracellular localization, and no relation between clinical stage and E-NPP3 expression were observed. Our results suggested that E-NPP3 is associated with carcinogenesis of human colon cancer and that serum E-NPP3 might be a tumor marker of colon carcinoma.
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PMID:Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-3 (E-NPP3/CD203c/PD-I beta/B10/gp130RB13-6) in human colon carcinoma. 1453 6

The ectonucleoside pyrophosphatase phosphodiesterase 1 (NPP1/PC-1) is a member of the NPP enzyme family that is critical in regulating mineralization. In certain mineralizing sites of bone and cartilage, membrane-limited vesicles [matrix vesicles (MVs)] provide a sheltered internal environment for nucleation of calcium-containing crystals, including hydroxyapatite. MV formation occurs by budding of vesicles from the plasma membrane of mineralizing cells. The MVs are enriched in proteins that promote mineralization. Paradoxically, NPP1, the type II transmembrane protein that generates the potent hydroxyapatite crystal growth inhibitor inorganic pyrophosphate (PP(i)), is also enriched in MVs. Although osteoblasts express NPP1, NPP2, and NPP3, only NPP1 is enriched in MVs. Therefore, this study uses mineralizing human osteoblastic SaOS-2 cells, a panel of NPP1 mutants, and NPP1 chimeras with NPP3, which does not concentrate in MVs, to investigate how NPP1 preferentially targets to MVs. We demonstrated that a cytosolic dileucine motif (amino acids 49-50) was critical in localizing NPP1 to regions of the plasma membrane that budded off into MVs. Moreover, transposition of the NPP1 cytoplasmic dileucine motif and flanking region (AAASLLAP) to NPP3 conferred to NPP3 the ability to target to the plasma membrane and, subsequently, concentrate in MVs. Functionally, the cytosolic tail dileucine motif NPP1 mutants lost the ability to support MV PP(i) concentrations and to suppress calcification. The results identify a specific targeting motif in the NPP1 cytosolic tail that delivers PP(i)-generating NPP activity to osteoblast MVs for control of calcification.
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PMID:Subcellular targeting and function of osteoblast nucleotide pyrophosphatase phosphodiesterase 1. 1507 17

Physiologic levels of extracellular PPi, which suppresses hydroxyapatite crystal growth, must be maintained by articular chondrocytes and resident cells in many othee tissues in order to prevent pathologic calcification. However, extracellular PPi rises in articular cartilage in direct association with aging. Matrix supersaturation with PPi stimulates chondrocalcinosis manifesting as calcium pyrophosphate dihydrate (CPPD) crystal deposition. Extracellular PPi levels are normally held in check by balances in PPi generation by nucleotide pyrophosphatase phosphodiesterase (NPP/NTPPPH) activity relative to PPi degradation by pyrophosphatases, by balance effects of cytokines and growth factors, and by transport of PPi from the cell interior involving the multiple-pass transmembrane protein ANK. But these mechanisms become dysrgulated in aging and osteoarthritic (OA) cartilage and extracellular PPi excess supervenes, mediated in large part by upregulated NPP1 and ANK expression in articular cartilage. Conversely, NPP1 and ANK deficiency states were recently linked to phenotypically similar forms of spontaneous soft tissue calcification with hydroxyapatite (HA). Here, we focus on recent advances in understanding of PPi metabolism and NPP1 and ANK function pertinent to the pathogenesis of pathologi matrix calcification in articular cartilage.
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PMID:Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage. 1556 37

Autotaxin (ATX) or nucleotide pyrophosphatase/phosphodiesterase 2 (NPP2) is an NPP family member that promotes tumor cell motility, experimental metastasis, and angiogenesis. ATX primarily functions as a lysophospholipase D, generating the lipid mediator lysophosphatidic acid (LPA) from lysophosphatidylcholine. ATX uses a single catalytic site for the hydrolysis of both lipid and non-lipid phosphodiesters, but its regulation is not well understood. Using a new fluorescence resonance energy transfer-based phosphodiesterase sensor that reports ATX activity with high sensitivity, we show here that ATX is potently and specifically inhibited by LPA and sphingosine 1-phosphate (S1P) in a mixed-type manner (Ki approximately 10(-7) M). The homologous ecto-phosphodiesterase NPP1, which lacks lysophospholipase D activity, is insensitive to LPA and S1P. Our results suggest that, by repressing ATX activity, LPA can regulate its own biosynthesis in the extracellular environment, and they reveal a novel role for S1P as an inhibitor of ATX, in addition to its well established role as a receptor ligand.
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PMID:Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. 1576 51

Neuroparsins (NPs) are small proteins that were originally discovered in the pars intercerebralis-corpus cardiacum neurosecretory complex of the migratory locust brain. From the desert locust, Schistocerca gregaria, we recently cloned four different transcripts, each coding for a distinct NP-related peptide. In addition to the brain, some NP-like precursor (Scg-NPP) transcripts also occur in a number of peripheral tissues, and their expression levels are controlled in a gender- and stage-dependent manner. Previous studies revealed a close correlation between Scg-NPP transcript levels and the gonotrophic cycle. In the present report, we demonstrate that certain Scg-NPP transcript levels are significantly altered upon injection of juvenile hormone (JH) or 20-hydroxyecdysone (20E) in adult gregarious desert locusts (five days after final ecdysis). While Scg-NPP1 transcript levels did not significantly change as a result of hormone treatment (animals were analyzed 24 h after injection), Scg-NPP2, Scg-NPP3, and Scg-NPP4 displayed hormone-dependent regulation in various tissues. Scg-NPP2 and Scg-NPP3 transcript levels significantly increased in the brain of JH-treated locusts. In addition, JH induction of Scg-NPP3 and Scg-NPP4 transcripts was observed in male fat body and in male and female gonads. Furthermore, 20E injection also induced Scg-NPP2, Scg-NPP3, and Scg-NPP4 transcripts in desert locust gonads. This is the first report showing NP-like precursor gene expression in insect ovaries. Our study indicates that the expression levels of some Scg-NPP transcripts are regulated by developmental hormones, suggesting a close correlation between NP expression and the endocrine control of the reproductive cycle.
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PMID:Regulation of Schistocerca gregaria neuroparsin transcript levels by juvenile hormone and 20-hydroxyecdysone. 1678 27

In the present study we investigate the biochemical properties of the members of NPP family in synaptosomes prepared from rat heart left ventricles. Using p-nitrophenyl-5'-thymidine monophosphate (p-Nph-5'-TMP) as substrate for E-NPPs in rat cardiac synaptosomes, we observed an alkaline pH dependence, divalent cation dependence and the K ( M ) value corresponded to 91.42 +/- 13.97 microM and the maximal velocity (V ( max )) value calculated was 63.79 +/- 3.59 nmol p-nitrophenol released/min/mg of protein (mean +/- SD, n = 4). Levamisole (1 mM), was ineffective as inhibitor of p-Nph-5'-TMP hydrolysis in pH 8.9 (optimum pH for the enzyme characterized). Suramin (0.25 mM) strongly reduced the hydrolysis of p-Nph-5'-TMP by about 46%. Sodium azide (10 and 20 mM) and gadolinium chloride (0.3 and 0.5 mM), E-NTPases inhibitors, had no effects on p-Nph-5'-TMP hydrolysis. RT-PCR analysis of left ventricle demonstrated the expression of NPP2 and NPP3 enzymes, but excluded the presence of NPP1 member. By quantitative real-time PCR we identified the NPP3 as the enzyme with the highest expression in rat left ventricle. The demonstration of the presence of the E-NPP family in cardiac system, suggest that these enzymes could contribute with the fine-tuning control of the nucleotide levels at the nerve terminal endings of left ventricles that are involved in several cardiac pathologies.
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PMID:Biochemical characterization of ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP, E.C. 3.1.4.1) from rat heart left ventricle. 1778 43

Extracellular nucleotides can elicit a wide array of cellular responses by binding to specific purinergic receptors. The level of ectonucleotides is dynamically controlled by their release from cells, synthesis by ectonucleoside diphosphokinases and ectoadenylate kinases, and hydrolysis by ectonucleotidases. One of the four structurally unrelated families of ectonucleotidases is represented by the NPP-type ectophosphodiesterases. Three of the seven members of the NPP family, namely NPP1-3, are known to hydrolyze nucleotides. The enzymatic action of NPP1-3 (in)directly results in the termination of nucleotide signaling, the salvage of nucleotides and/or the generation of new messengers like ADP, adenosine or pyrophosphate. NPP2 is unique in that it hydrolyzes both nucleotides and lysophospholipids and, thereby, generates products that could synergistically promote cell motility. We review here the enzymatic properties of NPPs and analyze current evidence that links their nucleotide-hydrolyzing capability to epithelial and neural functions, the immune response and cell motility.
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PMID:Modulation of purinergic signaling by NPP-type ectophosphodiesterases. 1840 76

The catabolism of ATP and other nucleotides participates partly in the important function of nucleotide salvage by activated cells and also in removal or de novo generation of compounds including ATP, ADP, and adenosine that stimulate purinergic signaling. Seven nucleotide pyrophosphatase/phosphodiesterase NPP family members have been identified to date. These isoenzymes, related by up conservation of catalytic domains and certain other modular domains, exert generally non-redundant functions via distinctions in substrates and/or cellular localization. But they share the capacity to hydrolyze phosphodiester or pyrophosphate bonds, though generally acting on distinct substrates that include nucleoside triphosphates, lysophospholipids and choline phosphate esters. PP(i) generation from nucleoside triphosphates, catalyzed by NPP1 in tissues including cartilage, bone, and artery media smooth muscle cells, supports normal tissue extracellular PP(i) levels. Balance in PP(i) generation relative to PP(i) degradation by pyrophosphatases holds extracellular PP(i) levels in check. Moreover, physiologic levels of extracellular PP(i) suppress hydroxyapatite crystal growth, but concurrently providing a reservoir for generation of pro-mineralizing P(i). Extracellular PP(i) levels must be supported by cells in mineralization-competent tissues to prevent pathologic calcification. This support mechanism becomes dysregulated in aging cartilage, where extracellular PP(i) excess, mediated in part by upregulated NPP1 expression stimulates calcification. PP(i) generated by NPP1modulates not only hydroxyapatite crystal growth but also chondrogenesis and expression of the mineralization regulator osteopontin. This review pays particular attention to the role of NPP1-catalyzed PP(i) generation in the pathogenesis of certain disorders associated with pathologic calcification.
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PMID:Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification. 1840 77


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