Abstract:
:The rat brain-derived neurotropic factor (BDNF) gene consists of four 5' exons linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. To gain insights into the regulation of BDNF mRNA expression, probes specific for the different 5' exons were used to study the expression of BDNF mRNA in the brain. Following a systemic injection of the glutamate analog kainic acid, exon I, II, and III mRNAs increased transiently in hippocampus and cerebral cortex. A modest increase was seen for exon IV, where a new transcription initiation site was induced by this treatment. Pretreatments with the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitrosulfanoylbenzo(f)quinoxaline revealed two region-specific patterns of glutamate receptor-mediated regulation. The first pattern found in neocortex, piriform cortex, and amygdala involves regulation of BDNF exon I, II, and III mRNAs through NMDA and AMPA/kainate receptors. The second pattern found in the hippocampus involves regulation of BDNF exon I, II, and III mRNAs by high-affinity kainate or metabotropic receptors. Treatment with the gamma-aminobutyric acid subtype A (GABAA) receptor antagonist bicuculline increased exon I and III mRNAs in the denate gyrus, and the muscarinic receptor agonist pilocarpine increased exon I mRNA mainly in the neocortex. These data show that the four BDNF promoters allow multiple points of BDNF mRNA regulation and suggest that the activation of different subtypes of glutamate receptors differentially regulates the expression of BDNF exon-specific mRNAs in the brain.
journal_name
Proc Natl Acad Sci U S Aauthors
Metsis M,Timmusk T,Arenas E,Persson Hdoi
10.1073/pnas.90.19.8802subject
Has Abstractpub_date
1993-10-01 00:00:00pages
8802-6issue
19eissn
0027-8424issn
1091-6490journal_volume
90pub_type
杂志文章abstract::The availability of gene-targeted mice deficient in the urokinase-type plasminogen activator (uPA), urokinase receptor (uPAR), tissue-type plasminogen activator (tPA), and plasminogen permits a critical, genetic-based analysis of the physiological and pathological roles of the two mammalian plasminogen activators. We ...
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.93.12.5899
更新日期:1996-06-11 00:00:00
abstract::For a constant membrane potential, a predominantly inhibitory GABAergic synaptic response is shown to undergo long-term transformation into an excitatory response after pairing of exogenous gamma-aminobutyric acid (GABA) with postsynaptic depolarization or pairing of pre- and postsynaptic stimulation. Current- and vol...
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.89.24.11862
更新日期:1992-12-15 00:00:00
abstract::The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subjec...
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.90.8.3710
更新日期:1993-04-15 00:00:00
abstract::The biological activity of the transcription factor NF-kappaB is differentially controlled by three IkappaB proteins, Ikappa Balpha, Ikappa Bbeta, and Ikappa Bepsilon. We have examined the molecular basis for the differential inhibitory strengths of IkappaB proteins by constructing hybrid IkappaBs and found that the f...
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.96.1.49
更新日期:1999-01-05 00:00:00
abstract::Selection is usually considered to be the dominant force controlling viral variation; the large population sizes suggest that deterministic population genetic models are appropriate. To investigate their validity for HIV, samples of env gene sequences were tested for departure from neutrality because of mutation-selec...
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.94.5.1862
更新日期:1997-03-04 00:00:00
abstract::In eukaryotic photosynthetic organisms, the conversion of solar into chemical energy occurs in thylakoid membranes in the chloroplast. How thylakoid membranes are formed and maintained is poorly understood. However, previous observations of vesicles adjacent to the stromal side of the inner envelope membrane of the ch...
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.1916946117
更新日期:2020-04-21 00:00:00
abstract::We have synthesized pulmonary surfactant apoprotein SP-B peptides by solid-phase chemistry and demonstrated their ability to enhance the surface-active properties of synthetic lipid mixtures. The synthetic peptides were reactive with antiserum generated against the native bovine surfactant peptide. Both peptides confe...
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.87.7.2633
更新日期:1990-04-01 00:00:00
abstract::A serum-free culture of dissociated neurons from embryonic rat hippocampus has been established as a rapid and quantitative in vitro test system for neurotrophic signals in the mammalian brain. By means of this cell culture bioassay, a novel low molecular weight neurotrophic factor (NTF) could be identified. NTF is es...
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.81.4.1248
更新日期:1984-02-01 00:00:00
abstract::A novel type I transmembrane protein of COPI-coated vesicles, p23, has been demonstrated to be localized mainly to the Golgi complex. This protein and p24, another member of the p24 family, have been shown to bind coatomer via their short cytoplasmic tails. Here we demonstrate that p23 continuously cycles through 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.94.21.11393
更新日期:1997-10-14 00:00:00
abstract::Evolution of new enzymatic activities is believed to require a period of gene sharing in which a single enzyme must serve both its original function and a new function that has become advantageous to the organism. Subsequent gene duplication allows one copy to maintain the original function, while the other diverges 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.0804804105
更新日期:2008-09-09 00:00:00
abstract::Establishing quantitative relationships between molecular structure and broad biological effects has been a longstanding challenge in science. Currently, no method exists for forecasting broad biological activity profiles of medicinal agents even within narrow boundaries of structurally similar molecules. Starting fro...
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.0407790101
更新日期:2005-01-11 00:00:00
abstract::Stimulated human monocytes release several proteins thought to play a role in inflammation, including interleukin 1, tumor necrosis factor, and plasminogen activator. We have purified another proinflammatory protein that is chemotactic for human neutrophils from conditioned medium of lipopolysaccharide-stimulated mono...
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.84.24.9233
更新日期:1987-12-01 00:00:00
abstract::Protein 2.1 is a 210-kilodalton protein that connects erythrocyte spectrin to the NH2-terminal cytoplasmic domain of band 3 and thereby functions as the essential linkage between the membrane skeleton and the bilayer. We cleaved this protein into specific chemical domains by limited digestion with trypsin and alpha-ch...
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.81.13.4095
更新日期:1984-07-01 00:00:00
abstract::Adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) deficiency is one cause of the genetic disease severe combined immunodeficiency. To identify mutations responsible for ADA deficiency, we synthesized cDNAs to ADA mRNAs from two cell lines, GM2756 and GM2825A, derived from ADA-deficient immunodeficient pa...
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.84.16.5947
更新日期:1987-08-01 00:00:00
abstract::Conjugative relaxases are the proteins that initiate bacterial conjugation by a site-specific cleavage of the transferred DNA strand. In vitro, they show strand-transferase activity on single-stranded DNA, which suggests they may also be responsible for recircularization of the transferred DNA. In this work, we show 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.0506081102
更新日期:2005-11-08 00:00:00
abstract::Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably 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.1505315112
更新日期:2015-08-25 00:00:00
abstract::DNA fragments encoding the mouse steroid 21-hydroxylase (C21 or Cyp21A1) gene are de novo methylated when introduced into the mouse adrenocortical tumor cell line Y1 by DNA-mediated gene transfer. Although CCGG sequences within the C21 gene are de novo methylated, CCGG sites within flanking vector sequences, other mam...
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.86.18.6853
更新日期:1989-09-01 00:00:00
abstract::Colocalization of proteins that are part of the same signal transduction pathway via compartmentalization, scaffold, or anchor proteins is an essential aspect of the signal transduction system in eukaryotic cells. If interaction must occur via free diffusion, then the spatial separation between the sources of the two ...
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.0401314101
更新日期:2004-04-27 00:00:00
abstract::Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. An acute increase in tumor oxygenation before radiation treatment should therefore significantly improve the tumor cell kill after radiation. Efforts to increase oxygen delivery to the tumor have not shown positiv...
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.1808945115
更新日期:2018-10-16 00:00:00
abstract::Understanding molecular mechanisms in the context of living cells requires the development of new methods of in vivo biochemical analysis to complement established in vitro biochemistry. A critically important molecular mechanism is genetic recombination, required for the beneficial reassortment of genetic information...
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.1424269112
更新日期:2015-08-25 00:00:00
abstract::Adenosine 3':5'-cyclic monophosphate added to exponentially growing cells of Hemophilus influenzae strain Rd increases competence for transformation 100- to 10,000-fold. Cyclic AMP added to near-stationary or stationary cells does not increase competence over the high level normally found in the early stationary phase...
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.70.2.471
更新日期:1973-02-01 00:00:00
abstract::The canonical function of the human telomerase protein (hTERT) is to synthesize telomeric DNA, but it has other biological activities, including enhancing cell proliferation, decreasing apoptosis, regulating DNA damage responses, and increasing cellular proliferative lifespan. The mechanistic relationships among these...
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.1112414108
更新日期:2011-12-13 00:00:00
abstract::Completely parthenogenetic Trichogramma wasps can be rendered permanently bisexual by treatment with three different antibiotics or high temperatures. The evidence strongly suggests that maternally inherited microorganisms cause parthenogenesis in these wasps. Theories predict female-biased sex ratio in offspring unde...
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.87.7.2424
更新日期:1990-04-01 00:00:00
abstract::Chorismate mutase acts at the first branch-point of aromatic amino acid biosynthesis and catalyzes the conversion of chorismate to prephenate. The results of molecular dynamics simulations of the substrate in solution and in the active site of chorismate mutase are reported. Two nonreactive conformers of chorismate ar...
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.141230998
更新日期:2001-07-31 00:00:00
abstract::When the dog kidney Na+/K+-transporting ATPase (EC 3.6.1.37, formerly EC 3.6.1.3) was labeled with an ATP analogue, 5'-(p-fluorosulfonyl)benzoyladenosine (FSBA), there was a concomitant loss of ATPase activity. The presence of ATP protected the enzyme from both labeling and inactivation. The ATP-sensitive incorporatio...
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.83.7.2071
更新日期:1986-04-01 00:00:00
abstract::Salivary gland cells in the larvae of the dipteran Chironomus tentans offer unique possibilities to visualize the assembly and nucleocytoplasmic transport of a specific transcription product. Each nucleus harbors four giant polytene chromosomes, whose transcription sites are expanded, or puffed. On chromosome IV, ther...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.111145498
更新日期:2001-06-19 00:00:00
abstract::The interaction of activated Ras with Raf initiates signaling cascades that contribute to a significant percentage of human tumors, suggesting that agents that specifically disrupt this interaction might have desirable chemotherapeutic properties. We used a subtractive forward two-hybrid approach to identify small mol...
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.222222699
更新日期:2002-10-29 00:00:00
abstract::The relationship between performance and ability is a central concern in the social sciences: Are the most successful much more able than others, and are failures unskilled? Prior research has shown that noise and self-reinforcing dynamics make performance unpredictable and lead to a weak association between ability a...
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.1116048109
更新日期:2012-06-12 00:00:00
abstract::Helodermin is a vasoactive intestinal peptide-like peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides ...
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.86.4.1357
更新日期:1989-02-01 00:00:00
abstract::The growth of 3T3 and SV101 3T3 cells in a lipid-depleted medium is enhanced by the addition of biotin or some fatty acids. The extent of enhancement depends on the fatty acid(s) supplied. The presence of linoleate is unique, since it induces a morphological alteration in 3T3 cells resulting in a cell similar to an SV...
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.71.8.3115
更新日期:1974-08-01 00:00:00