Primary structure of human placental 5′‐nucleotidase and identification of the glycolipid anchor in the mature form

Misumi, Yoshio; Ogata, Shigenori; Ohkubo, Kumiko; Hirose, Shinichi; Ikehara, Yukio

doi:10.1111/j.1432-1033.1990.tb19158.x

Cited by 147 publications

(111 citation statements)

References 43 publications

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“…Comparative enzyme assays revealed a higher potential for adenosine formation by way of the latter pathway. Transcripts recognized by a Two metabolic pathways participate in the production of adenosine: cellular transmethylation reactions mouse 5'-NT cRNA probe corresponded in size to the 3.9 kb band identified as 5'-NT mRNA in rat tissues (Misumi et al, 1990). They were detected in the uterus by day 4 of gestation and peaked in the embryo-decidual unit on day 5.…”

Section: Discussionmentioning

confidence: 98%

“…The mouse 5'-NT probe consisted of a 571 bp fragment amplified from poly(A+) RNA from the murine T lymphoma cell line, EL-4, by reverse transcriptase polymerase chain reaction (PCR) (Thompson and Park, unpublished). The primers (forward: 5'-GCGAATTCAGAGAGTGCAACA and reverse 5'-GTGGATCCTTCAACTGCTGGG) were synthesized based upon the published rat 5'-NT cDNA sequence (Misumi et al, 1990). The PCR product was cloned into pBluescript S K + (Stratagene, La Jolla, CAI and sequenced in both directions.…”

Section: Northern Blot Analysismentioning

confidence: 99%

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Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Blackburn

Gao

Airhart

et al. 1992

Developmental Dynamics

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Extracellular adenosine has the potential to influence many aspects of target cell metabolism. The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryodecidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5'-nucleotidase (5'-NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4). To measure adenosine levels, nucleoside extracts were etheno-derivatized and quantitated by high-performance liquid chromatography-fluorescence detection (0.03 pmollmg protein sensitivity). Adenosine levels were determined to be 0.18 nmol/mg protein in the nonpregnant uterus; however, two statistically significant changes were identified in the pregnant uterus: (1) a periimplantation surge between day 3 (0.24 nmoVmg protein) and day 5 (0.59 nmoYmg protein) of gestation (plug day 0; implantation day 4); and (2) an early postimplantation decline between day 6 (0.54 nmollmg protein) and day 7 (0.10 nmollmg protein). The periimplantation adenosine surge coincided with uterine expression of 5'-NT, an enzyme which catalyzes the irreversible dephosphorylation of 5'-AMP to adenosine. 5'-NT expression was shown by Northern blot analysis to peak in the embryo-decidual unit on day 5 of gestation and then to decline through day 9; transcripts remained elevated in the placenta between day 9 and day 13 (the latest day examined in this study). By use of specific enzyme histochemistry, most 5'-NT activity was localized to the primary decidual :zone on day 5. This expression subsequently declined during regression of the primary decidua; however, 5'-NT appeared on giant trophoblast ((days 7-13) and the metrial gland (days 11-13).Other purine catabolic enzymes degrading AMP (adenylate deaminase) or generating adenosine (S-adenosylhomocysteine hydrolase) were not detected in the embryo-decidual unit suggesting that the net flux of utero-placental AMP catabolism proceeds with adenosine as an intermediate, this being the major pathway of adenosine formation.The sharp drop in adenosine levels between day 6 and day 7 coincided with a rise in the activity and mRNA expression of ADA, an enzyme which catalyzes the irreversible deamination of adenosine to inosine. ADA was previously localized to the secondary decidual zone (days 6 1 l), secondary giant cells (days 7-13), and spongiotrophoblasts (days 8-13) in the mouse (Knudsen et al., 1991). Results of developmental Northern blot analysis demonstrated a direct correlation of relative 5'-NT/ADA mRNA band intensity to adenosine content between day 4 and day 9 of gestation, suggesting that the local availability of adenosine in the antimesometrium is dependent upon the distribution of these enzymatic activities. Purine nucleoside phosphorylase and xanthine oxidase, which are two catabolic enzymes acting subsequent to 5'-NT and ADA in the sequential degradation of AMP to xanthine, remained low and constant in the tissues examined suggesting that the catabolic pathway is geared toward regulation of adenosine le...

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Section: Discussionmentioning

confidence: 98%

Section: Northern Blot Analysismentioning

confidence: 99%

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Blackburn

Gao

Airhart

et al. 1992

Developmental Dynamics

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“…General molecular properties EN was first cloned from rat [237], human placenta [238], and the electric ray Torpedo electric organ [239], followed by identification of the cDNA sequence of a considerable variety of mammalian species [202,240]. The human cDNA encodes a precursor of 574 residues that is converted to the mature form of 523 residues after cleavage of the signal peptide and the hydrophobic domain at the C-terminus, which is replaced with the GPI anchor, similar to the enzymes cloned from rat [237] and mouse [204].…”

Section: Ecto-5′-nucleotidase Versus Soluble 5′-nucleotidasesmentioning

confidence: 99%

“…Using sequence information from isolated C-terminal fragments of the mature rat [255], human [238] and bovine [245] enzyme, it was shown that the GPI anchor is linked to the conserved Ser523 residue. The hydrophobic C-terminal extension is cleaved and replaced by GPI.…”

Section: Glycosylationmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

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922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…Other ecto-ATPases together with this enzyme form the cascade to finish the action of nucleotides such as ATP and extracellular signaling molecules acting on P2X and P2Y receptors. 5'-nucleotidase is present in basically all tissues and its primary structure has been determined in bovine and rat liver, electric ray brain, mouse kidney and human placenta, showing that the enzyme consists of 548 amino acids with a molecular mass varying between 62 and 74 kDa [90,105,128,135,144]. The protein occurs as a homodimer with interchain disulfide bridges and hydrolyzes a variety of nucleoside 5'-nucleoside monophosphates such as AMP, CMP, UMP, IMP and GMP.…”

Section: '-Nucleotidase: General Characteristicsmentioning

confidence: 99%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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Primary structure of human placental 5′‐nucleotidase and identification of the glycolipid anchor in the mature form

Cited by 147 publications

References 43 publications

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Cellular function and molecular structure of ecto-nucleotidases

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

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