当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Protease nexin-2/amyloid beta-protein precursor limits cerebral thrombosis.

Protease nexin-2/amyloid beta-protein precursor limits cerebral thrombosis.

Abstract：

:The amyloid beta-protein precursor (AbetaPP) is best known as the parent molecule to the amyloid beta-peptide that accumulates in the brains of patients with Alzheimer's disease. Secreted isoforms of AbetaPP that contain the Kunitz proteinase inhibitor domain are analogous to the previously identified cell-secreted proteinase inhibitor known as protease nexin-2 (PN2). Although PN2/AbetaPP is enriched in brain and in circulating blood platelets, little is understood of its physiological function and potential role in disease processes outside of amyloid beta-peptide generation. We hypothesized that the potent inhibition of certain procoagulant proteinases by PN2/AbetaPP, coupled with its abundance in platelets and brain, indicate that it may function to regulate cerebral thrombosis. Here we show that specific and modest 2-fold overexpression of PN2/AbetaPP in circulating platelets of transgenic mice caused a marked inhibition of thrombosis in vivo. In contrast, deletion of PN2/AbetaPP in AbetaPP gene knockout mice resulted in a significant increase in thrombosis. Similarly, platelet PN2/AbetaPP transgenic mice developed larger hematomas in experimental intracerebral hemorrhage, whereas AbetaPP gene knockout mice exhibited reduced hemorrhage size. These findings indicate that PN2/AbetaPP plays a significant role in regulating cerebral thrombosis and that modest increases in this protein can profoundly enhance cerebral hemorrhage.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Xu F,Davis J,Miao J,Previti ML,Romanov G,Ziegler K,Van Nostrand WE

doi

10.1073/pnas.0507798102

keywords:

subject

Has Abstract

pub_date

2005-12-13 00:00:00

pages

18135-40

issue

50

eissn

0027-8424

issn

1091-6490

pii

0507798102

journal_volume

102

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae.

    abstract：:The bacterial pathogen Streptococcus pneumoniae is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis, and septicemia. Available vaccines target only a subset of serotypes, so vaccination is often accompanied by a rise in the frequency of nonvaccine...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1718712115

    authors： Obolski U,Lourenço J,Thompson C,Thompson R,Gori A,Gupta S

    更新日期：2018-03-20 00:00:00

  • Molecular alteration in a Neurospora crassa morphological mutant and its phenocopy.

    abstract：:A procedure using ion exchange chromatography has been developed to detect alterations in a polysaccharide produced by Neurospora crassa. The polysaccharide, isolated from medium that has supported the growth of a culture, is highly responsive to the 3-methyl-2-benzothiazolinone hydrazone assay, indicating a high hexo...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.75.3.1461

    authors： Springer WD,Srb AM

    更新日期：1978-03-01 00:00:00

  • Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum.

    abstract：:Excess activation of glutamate receptors and production of free radicals including nitric oxide may result in severe and irreversible damage to the mammalian central nervous system (CNS), but endogenous defense systems that protect neurons from these insults are poorly understood. Here, we purified and isolated a neur...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.052693999

    authors： Kume T,Asai N,Nishikawa H,Mano N,Terauchi T,Taguchi R,Shirakawa H,Osakada F,Mori H,Asakawa N,Yonaga M,Nishizawa Y,Sugimoto H,Shimohama S,Katsuki H,Kaneko S,Akaike A

    更新日期：2002-03-05 00:00:00

  • Identification of a RNA polymerase II initiation site in the long terminal repeat of Moloney murine leukemia viral DNA.

    abstract：:We have used a soluble in vitro RNA polymerase II transcription system to define the site of initiation of Moloney murine leukemia viral RNA synthesis. Molecularly cloned integrated and unintegrated Moloney murine leukemia virus DNAs were used as templates. The 5' ends of in vitro transcripts and virion RNA of Moloney...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.78.9.5411

    authors： Fuhrman SA,Van Beveren C,Verma IM

    更新日期：1981-09-01 00:00:00

  • Odd-skipped related-1 controls neural crest chondrogenesis during tongue development.

    abstract：:The tongue is a critical element of the feeding system in tetrapod animals for their successful adaptation to terrestrial life. Whereas the oral part of the mammalian tongue contains soft tissues only, the avian tongue has an internal skeleton extending to the anterior tip. The mechanisms underlying the evolutionary d...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1306495110

    authors： Liu H,Lan Y,Xu J,Chang CF,Brugmann SA,Jiang R

    更新日期：2013-11-12 00:00:00

  • Adult and larval traits as determinants of geographic range size among tropical reef fishes.

    abstract：:Most marine organisms disperse via ocean currents as larvae, so it is often assumed that larval-stage duration is the primary determinant of geographic range size. However, empirical tests of this relationship have yielded mixed results, and alternative hypotheses have rarely been considered. Here we assess the relati...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1304074110

    authors： Luiz OJ,Allen AP,Robertson DR,Floeter SR,Kulbicki M,Vigliola L,Becheler R,Madin JS

    更新日期：2013-10-08 00:00:00

  • The C-terminal extension landscape of naturally presented HLA-I ligands.

    abstract：:HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides, and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential noncanonical binding modes, we collected in-depth and accurate HLA peptidomics da...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1717277115

    authors： Guillaume P,Picaud S,Baumgaertner P,Montandon N,Schmidt J,Speiser DE,Coukos G,Bassani-Sternberg M,Filippakopoulos P,Gfeller D

    更新日期：2018-05-15 00:00:00

  • A 40-y record reveals gradual Antarctic sea ice increases followed by decreases at rates far exceeding the rates seen in the Arctic.

    abstract：:Following over 3 decades of gradual but uneven increases in sea ice coverage, the yearly average Antarctic sea ice extents reached a record high of 12.8 × 106 km2 in 2014, followed by a decline so precipitous that they reached their lowest value in the 40-y 1979-2018 satellite multichannel passive-microwave record, 10...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1906556116

    authors： Parkinson CL

    更新日期：2019-07-16 00:00:00

  • An influenza A hemagglutinin small-molecule fusion inhibitor identified by a new high-throughput fluorescence polarization screen.

    abstract：:Influenza hemagglutinin (HA) glycoprotein is the primary surface antigen targeted by the host immune response and a focus for development of novel vaccines, broadly neutralizing antibodies (bnAbs), and therapeutics. HA enables viral entry into host cells via receptor binding and membrane fusion and is a validated targ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.2006893117

    authors： Yao Y,Kadam RU,Lee CD,Woehl JL,Wu NC,Zhu X,Kitamura S,Wilson IA,Wolan DW

    更新日期：2020-08-04 00:00:00

  • Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread.

    abstract：:Although microtubules (MTs) frequently form highly dynamic networks, subsets of MTs become stabilized in response to environmental cues and function as specialized tracks for vesicle and macromolecular trafficking. MT stabilization is controlled by specialized plus-end tracking proteins (+TIPs) whose accumulation at t...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1310760110

    authors： Naghavi MH,Gundersen GG,Walsh D

    更新日期：2013-11-05 00:00:00

  • General principles of attraction and competitive attraction as revealed by large-cage studies of moths responding to sex pheromone.

    abstract：:Knowledge of how insects are actually affected by sex pheromones deployed throughout a crop so as to disrupt mating has lacked a mechanistic framework sufficient for guiding optimization of this environmentally friendly pest-control tactic. Major hypotheses are competitive attraction, desensitization, and camouflage. ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0908453107

    authors： Miller JR,McGhee PS,Siegert PY,Adams CG,Huang J,Grieshop MJ,Gut LJ

    更新日期：2010-01-05 00:00:00

  • Length suppression in histone messenger RNA 3'-end maturation: processing defects of insertion mutant premessenger RNAs can be compensated by insertions into the U7 small nuclear RNA.

    abstract：:Efficient 3'-end processing of cell cycle-regulated mammalian histone premessenger RNAs (pre-mRNAs) requires an upstream stem-loop and a histone downstream element (HDE) that base pairs with the U7 small ribonucleoprotein. Insertions between these elements have two effects: the site of cleavage moves in concert with t...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.93.25.14659

    authors： Scharl EC,Steitz JA

    更新日期：1996-12-10 00:00:00

  • Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response.

    abstract：:General control nonderepressible 2 (GCN2) plays a major role in the cellular response to amino acid limitation. Although maintenance of amino acid homeostasis is critical for tumor growth, the contribution of GCN2 to cancer cell survival and proliferation is poorly understood. In this study, we generated GCN2 inhibito...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1805523115

    authors： Nakamura A,Nambu T,Ebara S,Hasegawa Y,Toyoshima K,Tsuchiya Y,Tomita D,Fujimoto J,Kurasawa O,Takahara C,Ando A,Nishigaki R,Satomi Y,Hata A,Hara T

    更新日期：2018-08-14 00:00:00

  • Transcriptional switch for programmed cell death in pith parenchyma of sorghum stems.

    abstract：:Pith parenchyma cells store water in various plant organs. These cells are especially important for producing sugar and ethanol from the sugar juice of grass stems. In many plants, the death of pith parenchyma cells reduces their stem water content. Previous studies proposed that a hypothetical D gene might be respons...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1807501115

    authors： Fujimoto M,Sazuka T,Oda Y,Kawahigashi H,Wu J,Takanashi H,Ohnishi T,Yoneda JI,Ishimori M,Kajiya-Kanegae H,Hibara KI,Ishizuna F,Ebine K,Ueda T,Tokunaga T,Iwata H,Matsumoto T,Kasuga S,Yonemaru JI,Tsutsumi N

    更新日期：2018-09-11 00:00:00

  • Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder.

    abstract：:Both stem cells and mast cells express c-kit and proliferate after exposure to c-kit ligand. Mutations in c-kit may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. These observations suggested to us that mastocytosis might in some patients...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.92.23.10560

    authors： Nagata H,Worobec AS,Oh CK,Chowdhury BA,Tannenbaum S,Suzuki Y,Metcalfe DD

    更新日期：1995-11-07 00:00:00

  • Stable three-dimensional metallic carbon with interlocking hexagons.

    abstract：:Design and synthesis of 3D metallic carbon that is stable under ambient conditions has been a long-standing dream. We predict the existence of such phases, T6- and T14-carbon, consisting of interlocking hexagons. Their dynamic, mechanical, and thermal stabilities are confirmed by carrying out a variety of state-of-the...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1311028110

    authors： Zhang S,Wang Q,Chen X,Jena P

    更新日期：2013-11-19 00:00:00

  • On the role of MHC class II molecules in the survival and lymphopenia-induced proliferation of peripheral CD4+ T cells.

    abstract：:CD4(+) T cells expand after transfer into lymphopenic H-2(b) A(beta)-/- mice (I-A(beta)-, I-E(alpha)-deficient mice) but not after transfer into lymphopenic MHC II(Delta/Delta) mice (I-A(alpha)-, I-A(beta)-, I-E(alpha)-, and I-E(beta)-deficient mice), implying that in H-2(b) A(beta)-/- mice, A(alpha) chain and E(beta)...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1037754100

    authors： Martin B,Bourgeois C,Dautigny N,Lucas B

    更新日期：2003-05-13 00:00:00

  • Act locally and think globally: intracerebral testosterone implants induce seasonal-like growth of adult avian song control circuits.

    abstract：:There is pronounced seasonal plasticity in the morphology of the neural circuits that regulate song behavior in adult songbirds, primarily in response to changes in plasma testosterone (T) levels. Most song nuclei have androgen receptors. Afferent input from the telencephalic nucleus HVc (also known as the "high vocal...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.192308799

    authors： Brenowitz EA,Lent K

    更新日期：2002-09-17 00:00:00

  • Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis.

    abstract：:This article demonstrates that a simple chemical model system, built by using a modular approach, may be used to predict the spatiotemporal dynamics of initiation of blood clotting in the complex network of hemostasis. Microfluidics was used to create in vitro environments that expose both the complex network and the ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0605560103

    authors： Kastrup CJ,Runyon MK,Shen F,Ismagilov RF

    更新日期：2006-10-24 00:00:00

  • A complex history of rearrangement in an orthologous region of the maize, sorghum, and rice genomes.

    abstract：:The sequences of large insert clones containing genomic DNA that is orthologous to the maize adh1 region were obtained for sorghum, rice, and the adh1-homoeologous region of maize, a remnant of the tetraploid history of the Zea lineage. By using all four genomes, it was possible to describe the nature, timing, and lin...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1434476100

    authors： Ilic K,SanMiguel PJ,Bennetzen JL

    更新日期：2003-10-14 00:00:00

  • Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns.

    abstract：:Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and sev...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0709121104

    authors： Jansen RK,Cai Z,Raubeson LA,Daniell H,Depamphilis CW,Leebens-Mack J,Müller KF,Guisinger-Bellian M,Haberle RC,Hansen AK,Chumley TW,Lee SB,Peery R,McNeal JR,Kuehl JV,Boore JL

    更新日期：2007-12-04 00:00:00

  • Secretion and autoproteolytic maturation of subtilisin.

    abstract：:The sequence of the cloned Bacillus amyloliquefaciens subtilisin gene suggested that this secreted serine protease is produced as a larger precursor, designated preprosubtilisin [Wells, J. A., Ferrari, E., Henner, D. J., Estell, D. A. & Chen, E. Y. (1983) Nucleic Acids Res. 11, 7911-7925]. Biochemical evidence present...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.83.10.3096

    authors： Power SD,Adams RM,Wells JA

    更新日期：1986-05-01 00:00:00

  • beta-Glucuronidase from Escherichia coli as a gene-fusion marker.

    abstract：:We have developed a gene-fusion system based on the Escherichia coli beta-glucuronidase gene (uidA). The uidA gene has been cloned from E. coli K-12 and its entire nucleotide sequence has been determined. beta-Glucuronidase has been purified to homogeneity and characterized. The enzyme has a subunit molecular weight o...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.83.22.8447

    authors： Jefferson RA,Burgess SM,Hirsh D

    更新日期：1986-11-01 00:00:00

  • Spin-orbital probes of biomolecular structure. A model DNA-acridine system.

    abstract：:Heavy atoms, such as bromine or iodine, perturb the excited-state properties of aromatic chromophores through a spin-orbital coupling mechanism. In the present work the use of specifically directed spin-orbital probes to study subtle structural relationships in biopolymers is described. Heavy atoms are introduced into...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.69.8.2198

    authors： Galley WC,Purkey RM

    更新日期：1972-08-01 00:00:00

  • SraL sRNA interaction regulates the terminator by preventing premature transcription termination of rho mRNA.

    abstract：:Transcription termination is a critical step in the control of gene expression. One of the major termination mechanisms is mediated by Rho factor that dissociates the complex mRNA-DNA-RNA polymerase upon binding with RNA polymerase. Rho promotes termination at the end of operons, but it can also terminate transcriptio...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1811589116

    authors： Silva IJ,Barahona S,Eyraud A,Lalaouna D,Figueroa-Bossi N,Massé E,Arraiano CM

    更新日期：2019-02-19 00:00:00

  • A mechanism for temporary bioadhesion.

    abstract：:The flatworm Macrostomum lignano features a duo-gland adhesive system that allows it to repeatedly attach to and release from substrates in seawater within a minute. However, little is known about the molecules involved in this temporary adhesion. In this study, we show that the attachment of M. lignano relies on the ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1814230116

    authors： Wunderer J,Lengerer B,Pjeta R,Bertemes P,Kremser L,Lindner H,Ederth T,Hess MW,Stock D,Salvenmoser W,Ladurner P

    更新日期：2019-03-05 00:00:00

  • A new class of Escherichia coli recBC mutants: implications for the role of RecBC enzyme in homologous recombination.

    abstract：:Mutants of Escherichia coli sensitive to phage T4 gene 2 mutants were obtained following ethyl methanesulfonate mutagenesis. By mapping and complementation analysis, the mutations in each of the six mutants are in recB and recC. By both in vivo and in vitro analyses, the nuclease activity of RecBC enzyme is undetectab...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.81.24.7850

    authors： Chaudhury AM,Smith GR

    更新日期：1984-12-01 00:00:00

  • Tuning and switching a DNA polymerase motor with mechanical tension.

    abstract：:Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced "tuning" and "switching." The internal conformational states of the enzyme motor are represented as nodes, and the ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1033134100

    authors： Goel A,Astumian RD,Herschbach D

    更新日期：2003-08-19 00:00:00

  • Dietary branched chain amino acids ameliorate injury-induced cognitive impairment.

    abstract：:Neurological dysfunction caused by traumatic brain injury results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes were investigated using lateral fl...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0910280107

    authors： Cole JT,Mitala CM,Kundu S,Verma A,Elkind JA,Nissim I,Cohen AS

    更新日期：2010-01-05 00:00:00

  • Regulatory architecture determines optimal regulation of gene expression in metabolic pathways.

    abstract：:In response to environmental changes, the connections ("arrows") in gene regulatory networks determine which genes modulate their expression, but the quantitative parameters of the network ("the numbers on the arrows") are equally important in determining the resulting phenotype. What are the objectives and constraint...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1114235109

    authors： Chubukov V,Zuleta IA,Li H

    更新日期：2012-03-27 00:00:00