Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice.


:Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease. In chimeric mice lacking iNOS in bone marrow (BM)-derived cells, PH was dependent on iNOS from BM-derived cells, whereas emphysema development was dependent on iNOS from non-BM-derived cells. Similar regulatory and structural alterations as seen in mouse lungs were found in lung tissue from humans with end-stage COPD.






Seimetz M,Parajuli N,Pichl A,Veit F,Kwapiszewska G,Weisel FC,Milger K,Egemnazarov B,Turowska A,Fuchs B,Nikam S,Roth M,Sydykov A,Medebach T,Klepetko W,Jaksch P,Dumitrascu R,Garn H,Voswinckel R,Kostin S,Seeger W,S




Has Abstract


2011-10-14 00:00:00
















  • Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin.

    abstract::Synaptotagmin is an abundant synaptic vesicle-associated protein proposed to be involved in calcium-mediated neurotransmitter release. Our molecular and genetic results demonstrate that, although synaptotagmin is required for the proper function of the presynaptic nerve terminal in C. elegans, some neurotransmitter re...


    pub_type: 杂志文章


    authors: Nonet ML,Grundahl K,Meyer BJ,Rand JB

    更新日期:1993-07-02 00:00:00

  • Trans-acting nuclear protein responsible for induction of rearranged human immunoglobulin heavy chain gene.

    abstract::A complete human gamma 1 heavy chain gene (HIG1) was transferred into mouse cells by protoplast fusion. The HIG1 gene was strongly expressed in mouse myeloma cells but not in mouse fibroblasts (L cells). Nuclear extracts from myeloma cells were injected into L cell transformants containing one copy of the HIG1 gene; t...


    pub_type: 杂志文章


    authors: Maeda H,Kitamura D,Kudo A,Araki K,Watanabe T

    更新日期:1986-04-11 00:00:00

  • Meiotic proteins bqt1 and bqt2 tether telomeres to form the bouquet arrangement of chromosomes.

    abstract::In many organisms, meiotic chromosomes are bundled at their telomeres to form a "bouquet" arrangement. The bouquet formation plays an important role in homologous chromosome pairing and therefore progression of meiosis. As meiotic telomere clustering occurs in response to mating pheromone signaling in fission yeast, w...


    pub_type: 杂志文章


    authors: Chikashige Y,Tsutsumi C,Yamane M,Okamasa K,Haraguchi T,Hiraoka Y

    更新日期:2006-04-07 00:00:00

  • cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor.

    abstract::Using immobilized PDGF receptor as an affinity reagent, we purified an 85 kd protein (p85) from cell lysates and we cloned its cDNA. The protein contains an SH3 domain and two SH2 domains that are homologous to domains found in several receptor-associated enzymes. Recombinant p85 overexpressed in mammalian cells inhib...


    pub_type: 杂志文章


    authors: Escobedo JA,Navankasattusas S,Kavanaugh WM,Milfay D,Fried VA,Williams LT

    更新日期:1991-04-05 00:00:00

  • Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation.

    abstract::A key step in the regulation of transcription involves interactions between promoter-selective factors and various components of the transcriptional apparatus. Here we report the requirements for transcriptional activation directed by NTF-1, a developmentally regulated transcription factor in Drosophila. Reconstituted...


    pub_type: 杂志文章


    authors: Dynlacht BD,Hoey T,Tjian R

    更新日期:1991-08-09 00:00:00

  • Organoid models of human and mouse ductal pancreatic cancer.

    abstract::Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tiss...


    pub_type: 杂志文章


    authors: Boj SF,Hwang CI,Baker LA,Chio II,Engle DD,Corbo V,Jager M,Ponz-Sarvise M,Tiriac H,Spector MS,Gracanin A,Oni T,Yu KH,van Boxtel R,Huch M,Rivera KD,Wilson JP,Feigin ME,Öhlund D,Handly-Santana A,Ardito-Abraham CM,L

    更新日期:2015-01-15 00:00:00

  • Sir2 blocks extreme life-span extension.

    abstract::Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack ...


    pub_type: 杂志文章


    authors: Fabrizio P,Gattazzo C,Battistella L,Wei M,Cheng C,McGrew K,Longo VD

    更新日期:2005-11-18 00:00:00

  • Incomplete arrest in the outer membrane sorts NADH-cytochrome b5 reductase to two different submitochondrial compartments.

    abstract::The S. cerevisiae gene MCR1 encodes two mitochondrial isoforms of NADH-cytochrome b5 reductase. The primary translation product has an amino-terminal matrix-targeting signal, followed by a stretch of 21 uncharged amino acids. This precursor protein is inserted into the outer membrane, but only about one-third of the m...


    pub_type: 杂志文章


    authors: Hahne K,Haucke V,Ramage L,Schatz G

    更新日期:1994-12-02 00:00:00

  • Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.

    abstract::Cell-cell junctions respond to mechanical forces by changing their organization and function. To gain insight into the mechanochemical basis underlying junction mechanosensitivity, we analyzed tight junction (TJ) formation between the enveloping cell layer (EVL) and the yolk syncytial layer (YSL) in the gastrulating z...


    pub_type: 杂志文章


    authors: Schwayer C,Shamipour S,Pranjic-Ferscha K,Schauer A,Balda M,Tada M,Matter K,Heisenberg CP

    更新日期:2019-10-31 00:00:00

  • Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells.

    abstract::Enteropathogenic E. coli (EPEC) belongs to a group of bacterial pathogens that induce epithelial cell actin rearrangements resulting in pedestal formation beneath adherent bacteria. This requires the secretion of specific virulence proteins needed for signal transduction and intimate adherence. EPEC interaction induce...


    pub_type: 杂志文章


    authors: Kenny B,DeVinney R,Stein M,Reinscheid DJ,Frey EA,Finlay BB

    更新日期:1997-11-14 00:00:00

  • A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity.

    abstract::Fos and Jun transcription factors are induced by a variety of extracellular signaling agents. We describe here an unusual member of the Fos family that is also induced, namely, a truncated form of FosB (delta FosB) missing the C-terminal 101 amino acids of FosB. delta FosB retains the dimerization and DNA-binding acti...


    pub_type: 杂志文章


    authors: Nakabeppu Y,Nathans D

    更新日期:1991-02-22 00:00:00

  • TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene.

    abstract::Yeast chromosomes terminate in tracts of simple repetitive DNA (poly[G1-3T]). Mutations in the gene TEL1 result in shortened telomeres. Sequence analysis of TEL1 indicates that it encodes a very large (322 kDa) protein with amino acid motifs found in phosphatidylinositol/protein kinases. The closest homolog to TEL1 is...


    pub_type: 杂志文章


    authors: Greenwell PW,Kronmal SL,Porter SE,Gassenhuber J,Obermaier B,Petes TD

    更新日期:1995-09-08 00:00:00

  • Cis-acting induction of adenovirus transcription.

    abstract::At early times after adenovirus infection, transcription from all early viral promoters requires the expression of a 289 amino acid phosphoprotein encoded in the pre-early transcription unit E1A. Mutations in E1A result in a marked delay in the induction of early viral transcription. To distinguish between possible mo...


    pub_type: 杂志文章


    authors: Gaynor RB,Berk AJ

    更新日期:1983-07-01 00:00:00

  • Factor-independent termination of transcription in a stretch of deoxyadenosine residues in the template DNA.

    abstract::The primer transcript of plasmid ColE1 extends beyond the replication origin in either of two different modes. It does or does not form a hybrid with the template DNA. When a stretch of 20 deoxyadenosine residues is inserted into the template strand downstream of the origin, more than 90% of hybridized transcripts and...


    pub_type: 杂志文章


    authors: Tomizawa J,Masukata H

    更新日期:1987-11-20 00:00:00

  • Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient.

    abstract::Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We ...


    pub_type: 杂志文章


    authors: Müller B,Hartmann B,Pyrowolakis G,Affolter M,Basler K

    更新日期:2003-04-18 00:00:00

  • Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism.

    abstract::NF-kappa B is a nuclear protein, found only in cells that transcribe immunoglobulin light chain genes, that interacts with a defined site in the kappa immunoglobulin enhancer. This protein can be induced in pre-B cells by stimulation with bacterial lipopolysaccharide (LPS). The induction involves a posttranslational a...


    pub_type: 杂志文章


    authors: Sen R,Baltimore D

    更新日期:1986-12-26 00:00:00

  • Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease.

    abstract::Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accu...


    pub_type: 杂志文章


    authors: Xu Z,Cork LC,Griffin JW,Cleveland DW

    更新日期:1993-04-09 00:00:00

  • FoxOs in tumor suppression and stem cell maintenance.

    abstract::The FoxO transcription factors have been implicated in many processes including tumor suppression and cell death. In this issue, two groups now report on mice that conditionally lack the three predominant FoxO transcription factors. Demonstrate that FoxOs are critical for the long-term maintenance of hematopoietic ste...


    pub_type: 评论,杂志文章,评审


    authors: Arden KC

    更新日期:2007-01-26 00:00:00

  • Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex.

    abstract::The Origin Recognition Complex (ORC) is a six-protein assembly that specifies the sites of DNA replication initiation in S. cerevisiae. Origin recognition by ORC requires ATP. Here, we demonstrate that two subunits, Orc1p and Orc5p, bind ATP and that Orc1p also hydrolyzes ATP. ATP binding and hydrolysis by Orc1p are b...


    pub_type: 杂志文章


    authors: Klemm RD,Austin RJ,Bell SP

    更新日期:1997-02-21 00:00:00

  • Bacterial bioluminescence: isolation and genetic analysis of functions from Vibrio fischeri.

    abstract::Recombinant E. coli that produce light were found in a clone library of hybrid plasmids containing DNA from the marine bacterium Vibrio fischeri. All luminescent clones had a 16 kb insert that encoded enzymatic activities for the light reaction as well as regulatory functions necessary for expression of the luminescen...


    pub_type: 杂志文章


    authors: Engebrecht J,Nealson K,Silverman M

    更新日期:1983-03-01 00:00:00

  • Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum.

    abstract::The subcellular localization of the mouse Ltk transmembrane protein tyrosine kinase was studied in transfected COS cells, a mature B lymphocyte line, and a low expressing transfected lymphocyte clone. Indirect immunofluorescence and immunogold staining of COS transfectants and endoglycosidase analysis of both COS tran...


    pub_type: 杂志文章


    authors: Bauskin AR,Alkalay I,Ben-Neriah Y

    更新日期:1991-08-23 00:00:00

  • Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

    abstract::Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previ...


    pub_type: 杂志文章


    authors: Wu X,Dao Thi VL,Huang Y,Billerbeck E,Saha D,Hoffmann HH,Wang Y,Silva LAV,Sarbanes S,Sun T,Andrus L,Yu Y,Quirk C,Li M,MacDonald MR,Schneider WM,An X,Rosenberg BR,Rice CM

    更新日期:2018-01-25 00:00:00

  • RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.

    abstract::Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited, typically adult onset, polyglutamine neurodegenerative diseases. To examine whether development impacts SCA1, we used a conditional transgenic mouse model of SCA1 to delay the postnatal expression of mutant ATXN1 until after completion of cerebellar develo...


    pub_type: 杂志文章


    authors: Serra HG,Duvick L,Zu T,Carlson K,Stevens S,Jorgensen N,Lysholm A,Burright E,Zoghbi HY,Clark HB,Andresen JM,Orr HT

    更新日期:2006-11-17 00:00:00

  • The role of RNA molecules in transduction of the proto-oncogene c-fps.

    abstract::Transduction of cellular genes by retroviruses requires two recombinations: one to form the left-hand junction between cellular gene and viral genome, the other to form the right-hand junction. Previous findings raised the possibility that the right-hand recombination might use RNA molecules as intermediates. We now p...


    pub_type: 杂志文章


    authors: Huang CC,Hay N,Bishop JM

    更新日期:1986-03-28 00:00:00

  • An extracellular chemical signal controlling phototactic behavior by D. discoideum slugs.

    abstract::Developing cells of the cellular slime mold Dictyostelium discoideum release a low molecular weight metabolite (Slug Turning Factor, STF) which, at high uniform concentrations, interferes with phototaxis and thermotaxis by D. discoideum slugs. D. discoideum slugs migrating in darkness are repelled by (exhibit negative...


    pub_type: 杂志文章


    authors: Fisher PR,Smith E,Williams KL

    更新日期:1981-03-01 00:00:00

  • Mouse development and cell proliferation in the absence of D-cyclins.

    abstract::D-type cyclins (cyclins D1, D2, and D3) are regarded as essential links between cell environment and the core cell cycle machinery. We tested the requirement for D-cyclins in mouse development and in proliferation by generating mice lacking all D-cyclins. We found that these cyclin D1(-/-)D2(-/-)D3(-/-) mice develop u...


    pub_type: 杂志文章


    authors: Kozar K,Ciemerych MA,Rebel VI,Shigematsu H,Zagozdzon A,Sicinska E,Geng Y,Yu Q,Bhattacharya S,Bronson RT,Akashi K,Sicinski P

    更新日期:2004-08-20 00:00:00

  • Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif.

    abstract::We have adopted Drosophila tissue culture cells as a host system for studying the structure and function of mammalian transcription factors. These cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1. The SV40 early pro...


    pub_type: 杂志文章


    authors: Courey AJ,Tjian R

    更新日期:1988-12-02 00:00:00

  • CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate.

    abstract::We have isolated and characterized a set of overlapping cDNA clones that encode the human centromere autoantigen centromere protein C (CENP-C). The identity of these clones has been established using several criteria. First, they were shown to encode a polypeptide that migrates at the expected position for CENP-C on S...


    pub_type: 杂志文章


    authors: Saitoh H,Tomkiel J,Cooke CA,Ratrie H 3rd,Maurer M,Rothfield NF,Earnshaw WC

    更新日期:1992-07-10 00:00:00

  • RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway.

    abstract::Type I interferons (IFNs) are important for antiviral and autoimmune responses. Retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral signaling (MAVS) proteins mediate IFN production in response to cytosolic double-stranded RNA or single-stranded RNA containing 5'-triphosphate (5'-ppp). Cytosolic B form dou...


    pub_type: 杂志文章


    authors: Chiu YH,Macmillan JB,Chen ZJ

    更新日期:2009-08-07 00:00:00

  • p53 regulation orchestrates the TGF-beta response.

    abstract::Among its multiple functions, p53 is a critical regulator of TGF-beta responses. Sasai et al. (2008) now identify a new p53 inhibitory protein, XFDL156. During embryonic development, this factor is expressed in the ectoderm germ layer and maintains the pluripotency of ectodermal cells by inhibiting TGF-beta target gen...


    pub_type: 评论,杂志文章


    authors: Piccolo S

    更新日期:2008-05-30 00:00:00