Abstract:
:Transcriptional activation of cytochrome P450 (CYP) genes and various drug metabolizing enzymes by the prototypical inducer phenobarbital (PB) and many other drugs and chemicals is an adaptive response of the organism to exposure to xenobiotics. The response to PB is mediated by the nuclear receptor constitutive androstane receptor (CAR), whereas the chicken xenobiotic receptor (CXR) has been characterized as the PB mediator in chicken hepatocytes. Our previous results suggested an involvement of AMP-activated protein kinase (AMPK) in the molecular mechanism of PB induction. Here, we show that the mechanism of AMPK activation is related to an effect of PB-type inducers on mitochondrial function with consequent formation of reactive oxygen species (ROS) and phosphorylation of AMPK by the upstream kinase LKB1. Gain- and loss-of-function experiments demonstrate that LKB1-activated AMPK is necessary in the mechanism of drug induction and that this is an evolutionary conserved pathway for detoxification of exogenous and endogenous chemicals. The activation of LKB1 adds a proximal target to the so far elusive sequence of events by which PB and other drugs induce the transcription of multiple genes.
journal_name
Proc Natl Acad Sci U S Aauthors
Blättler SM,Rencurel F,Kaufmann MR,Meyer UAdoi
10.1073/pnas.0610216104subject
Has Abstractpub_date
2007-01-16 00:00:00pages
1045-50issue
3eissn
0027-8424issn
1091-6490pii
0610216104journal_volume
104pub_type
杂志文章abstract::We have screened a human DNA library using as probe a chimpanzee sequence that contains homology to the polymerase gene of the endogenous baboon virus. One set of overlapping clones spans about 20 kilobases and contains regions of DNA sequence homology to the gag p30, gag p15, and polymerase genes of Moloney murine le...
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.79.15.4709
更新日期:1982-08-01 00:00:00
abstract::Constitutive cyclooxygenase (COX-1; prostaglandin-endoperoxide synthase, EC 1.14.99.1) is present in cells under physiological conditions, whereas COX-2 is induced by some cytokines, mitogens, and endotoxin presumably in pathological conditions, such as inflammation. Therefore, we have assessed the relative inhibitory...
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.90.24.11693
更新日期:1993-12-15 00:00:00
abstract::The productivity of aquatic ecosystems depends on the supply of limiting nutrients. The invasion of the Laurentian Great Lakes, the world's largest freshwater ecosystem, by dreissenid (zebra and quagga) mussels has dramatically altered the ecology of these lakes. A key open question is how dreissenids affect the cycli...
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.2008223118
更新日期:2021-02-09 00:00:00
abstract::Classical studies suggest that high-level cognitive decisions (e.g., choosing between financial options) are suboptimal. In contrast, low-level decisions (e.g., choosing where to put your feet on a rocky ridge) appear near-optimal: the perception-cognition gap. Moreover, in classical tasks, people appear to put too mu...
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.1300239110
更新日期:2013-10-01 00:00:00
abstract::High-resolution maps integrated with the enhanced location data base software (LDB+) give improved estimates of genetic parameters and reveal characteristics of cytogenetic bands. Chiasma interference is intermediate between Kosambi and Carter-Falconer levels, as in Drosophila and the mouse. The autosomal genetic map ...
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.93.25.14771
更新日期:1996-12-10 00:00:00
abstract::The tissue-specific, cell-aggregating component of embryonic neural retina cells was purified from the retina cell-aggregating factor and characterized as a glycoprotein. Its molecular weight in solution is in the range of 50,000, and it contains 10-15% carbohydrate. The amino-acid and carbohydrate compositions have b...
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.72.3.916
更新日期:1975-03-01 00:00:00
abstract::The clonal rat pituitary cell line GH4C1 expresses the genes for several voltage-dependent potassium channels including Kv1.5 and Kv1.4. Dexamethasone, a glucocorticoid agonist, induces a slowly inactivating potassium current in these cells but does not alter the amplitude of a rapidly inactivating component of potass...
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.92.13.5955
更新日期:1995-06-20 00:00:00
abstract::Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in the collective organization of nucleosomes in vivo than previously thought. Yet in living cells, this organization also results from the action of various external factors like 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.0909511106
更新日期:2009-12-29 00:00:00
abstract::A 600-base-pair region essential for ColE1 and pMBl plasmid replication contains two promoters responsible for the synthesis of two RNA molecules central to copy number control. One promoter directs synthesis of the primer RNA precursor. The second promoter directs the synthesis of a small RNA molecule, RNAl, which ac...
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.79.20.6313
更新日期:1982-10-01 00:00:00
abstract::The livers of insulin-resistant, diabetic mice manifest selective insulin resistance, suggesting a bifurcation in the insulin signaling pathway: Insulin loses its ability to block glucose production (i.e., it fails to suppress PEPCK and other genes of gluconeogenesis), yet it retains its ability to stimulate fatty aci...
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.0914798107
更新日期:2010-02-23 00:00:00
abstract::Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+) store depletion. Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting 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.051632698
更新日期:2001-03-13 00:00:00
abstract::Nuclear RNA of high molecular weight, approximately 15 to 30 x 10(3) nucleotides long, isolated from rat ascites cells, has been shown previously to contain both middle repetitive and single-copy sequences. However, it was not known whether these sequences were located on separate molecules or whether they were inters...
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.71.4.1108
更新日期:1974-04-01 00:00:00
abstract::cDNA fragments of the homologues of the Drosophila head homeotic genes labial (lab), proboscipedia (pb), and Deformed (Dfd) have been isolated from the crustacean Porcellio scaber. Because the accumulation domains of the head homeotic complex (Hox) genes had not been previously reported for crustaceans, we studied 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.96.18.10224
更新日期:1999-08-31 00:00:00
abstract::Phosphoinositides are essential lipid regulators of trafficking and signaling pathways of all eukaryotic cells. Phosphatidylinositol 4-phosphate (PtdIns4P) is an intermediate in the synthesis of several important phosphoinositide species but also serves as a regulatory molecule in its own right. Phosphatidylinositol 4...
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.1000157107
更新日期:2010-05-04 00:00:00
abstract::Free gangliosides bind fibroblast growth factor 2 (FGF2), thus preventing cell interaction and biological activity of the growth factor in endothelial cells. Here we investigated the role of cell-associated gangliosides in mediating the biological activity of FGF2. Treatment of endothelial cells of different origin wi...
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.072651899
更新日期:2002-04-02 00:00:00
abstract::Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and the glutathione-dependent form...
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.89.19.9247
更新日期:1992-10-01 00:00:00
abstract::We have studied the effects of specific ligands of the receptor for the IgG Fc fragment (FcR) on the membrane potential (delta psi) of the macrophage cell line J774 by the [3H]tetraphenylphosphonium ion equilibration technique. We observe a membrane depolarization with binding of FcR ligands that is dependent on the 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.80.5.1357
更新日期:1983-03-01 00:00:00
abstract::The liver plays a key role in the regulation of circulating levels of low density lipoproteins (LDL) because it is both the site for the production of and the major organ for the degradation of this class of lipoproteins. In this study, the effects of feeding polyunsaturated or saturated triacylglycerols on receptor-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.82.13.4526
更新日期:1985-07-01 00:00:00
abstract::Homologous recombination is an important biological process that occurs in all organisms and facilitates genome rearrangements and repair of DNA double-strand breaks. Eukaryotic Rad51 proteins (Rad51sp or Rhp51 in fission yeast) are functional and structural homologs of bacterial RecA protein, an evolutionarily conser...
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.2632890100
更新日期:2003-12-23 00:00:00
abstract::Soil organisms, as recorded by trace fossils in paleosols of the Willwood Formation, Wyoming, show significant body-size reductions and increased abundances during the Paleocene-Eocene Thermal Maximum (PETM). Paleobotanical, paleopedologic, and oxygen isotope studies indicate high temperatures during the PETM and shar...
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.0909674106
更新日期:2009-10-20 00:00:00
abstract::Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at ...
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.1201280109
更新日期:2012-07-03 00:00:00
abstract::Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles...
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.1300684110
更新日期:2013-05-21 00:00:00
abstract::It is suggested that differentiated embryonic cells have a high specificity of molecular constitution as regards the surface layers surrounding their cellular membranes. Correspondingly, specific interface energies may characterize the early contacts between different cell types. The question is raised whether the mor...
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.67.1.156
更新日期:1970-09-01 00:00:00
abstract::Recombinant immunotoxins (RITs) are chimeric proteins composed of an Fv and a protein toxin being developed for cancer treatment. The Fv brings the toxin to the cancer cell, but most of the RITs do not reach the tumor and are removed by other organs. To identify cells responsible for RIT removal, and the pathway by wh...
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.1919038117
更新日期:2020-03-17 00:00:00
abstract::The "kindling" phenomenon is associated with long-lasting facilitation of synaptic transmission. A possible mechanism of such facilitation could involve changes in the number of synaptic contacts. However, previous attempts to demonstrate a synaptic morphological alteration that could account for the long-term effects...
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.85.9.3260
更新日期:1988-05-01 00:00:00
abstract::A polypeptide was isolated from acid extracts of porcine hypothalami on the basis of its high ability to stimulate the release of corticotropin from superfused rat pituitary cells. After an initial separation by gel filtration on Sephadex G-25, further purification was carried out by reversed-phase HPLC. The isolated ...
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.82.24.8762
更新日期:1985-12-01 00:00:00
abstract::Many fatal neurodegenerative diseases such as Alzheimer's, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. We have discovered that a class of systematically designe...
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.1014796108
更新日期:2011-01-25 00:00:00
abstract::The persistent tetrodotoxin (TTX)-sensitive sodium current, detected in neurons of many regions of mammalian brains, is associated with many essential neuronal activities, including boosting of excitatory synaptic inputs, acceleration of firing rates, and promotion of oscillatory neuronal activities. However, the orig...
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.0307695101
更新日期:2004-08-10 00:00:00
abstract::The coordinated redistribution of sugars from mature "source" leaves to developing "sink" leaves requires tight regulation of sugar transport between cells via plasmodesmata (PD). Although fundamental to plant physiology, the mechanisms that control PD transport and thereby support development of new leaves have remai...
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.1919196117
更新日期:2020-03-03 00:00:00
abstract::Conformist bias occurs when the probability of adopting a more common cultural variant in a population exceeds its frequency, and anticonformist bias occurs when the reverse is true. Conformist and anticonformist bias have been widely documented in humans, and conformist bias has also been observed in many nonhuman an...
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.2004102117
更新日期:2020-06-16 00:00:00