Functional roles of fructose.

Abstract:

:During the periimplantation period of pregnancy, pig blastocysts undergo morphological changes and differentiation requiring secretion and transport of nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although glucose is an energy source for proliferation and growth of mammalian cells, the role of fructose in uterine histotroph is unclear although it is the most abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows, sheep, and pigs). In this study, we used porcine trophectoderm cells to determine that fructose increased cell proliferation, as did glucose. Western blot analyses of porcine trophectoderm cell extracts revealed that fructose increased the abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within 30 min, and those levels remained elevated to 120 min. Phosphorylation of both RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1) and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response to fructose is mediated via GFPT1 activation and the hexosamine pathway. We further demonstrated that fructose stimulates the production of hyaluronic acid via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results demonstrate critical roles for fructose that are mediated via the hexosamine biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine trophectoderm cells, and synthesis of hyaluronic acid, a significant glycosaminoglycan in the pregnant uterus.

authors

Kim J,Song G,Wu G,Bazer FW

doi

10.1073/pnas.1204298109

subject

Has Abstract

pub_date

2012-06-19 00:00:00

pages

E1619-28

issue

25

eissn

0027-8424

issn

1091-6490

pii

1204298109

journal_volume

109

pub_type

杂志文章
  • Glucocorticoid and cAMP induction mechanisms are differentially affected by the p85gag-mos oncoprotein.

    abstract::The inability to perceive and coordinate both internal and external signals that function to regulate cellular growth and proliferation is a hallmark of oncogenic transformation. To examine the effects of the v-mos oncogene on distinct signal transduction pathways, the 6m2 cell line was used, in which expression of th...

    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.86.2.597

    authors: Hamilton BJ,DeFranco D

    更新日期:1989-01-01 00:00:00

  • Role of the nonheme Fe(II) center in the biosynthesis of the plant hormone ethylene.

    abstract::The final step of ethylene biosynthesis in plants is catalyzed by the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO). In addition to ACC, Fe(II), O2, CO2, and ascorbate are required for in vitro enzyme activity. Direct evidence for the role of the Fe(II) center in the recombinant avocado ACCO has no...

    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.96.14.7905

    authors: Rocklin AM,Tierney DL,Kofman V,Brunhuber NM,Hoffman BM,Christoffersen RE,Reich NO,Lipscomb JD,Que L Jr

    更新日期:1999-07-06 00:00:00

  • RNA-directed DNA polymerase and virus-induced leukemia in mice.

    abstract::Rifamycin antibiotics, which inhibit RNA-directed DNA polymerase of Rauscher leuckemia virus, prevent the leukemogenic activity of the virus, and the effect of leukemogenesis correlates with the magnitude of inhibition of the purified enzyme. This inhibition of enzyme activity by rifamycin SV derivatives is due to a r...

    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.70.5.1298

    authors: Wu AM,Ting RC,Gallo RC

    更新日期:1973-05-01 00:00:00

  • Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein.

    abstract::Glycoprotein Ib is a surface membrane glycoprotein of platelets that functions as a receptor for von Willebrand factor. It is a heterodimer composed of an alpha and a beta chain linked by a disulfide bond(s). A phage lambda gt11 cDNA expression library prepared from mRNA from a human erythroleukemia cell line, HEL, wa...

    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.84.16.5615

    authors: Lopez JA,Chung DW,Fujikawa K,Hagen FS,Papayannopoulou T,Roth GJ

    更新日期:1987-08-01 00:00:00

  • Functional dissection of the transmitter module of the histidine kinase NtrB in Escherichia coli.

    abstract::Signal transduction by two-component systems involves phosphorylation and thereby activation of the response regulator by the cognate histidine kinase. Bifunctional histidine kinases have two opposing activities: depending on the environmental stimuli they either promote phosphorylation or stimulate the rapid dephosph...

    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.96.2.604

    authors: Kramer G,Weiss V

    更新日期:1999-01-19 00:00:00

  • An attempt to locate the non-helical and permissively helical sequences of proteins: application to the variable regions of immunoglobulin light and heavy chains.

    abstract::From a consideration of (varphi, Psi) values of the amino acids of myoglobin, lysozyme, the alpha and beta chains of horse oxyhemoglobin, tosyl-alpha-chymotrypsin, and carboxypeptidase A, an empirical procedure of predicting whether amino-acid residues in proteins are in a non-helical or may be in a helical conformati...

    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.68.7.1501

    authors: Wu TT,Kabat EA

    更新日期:1971-07-01 00:00:00

  • Substrate activation for O2 reactions by oxidized metal centers in biology.

    abstract::The uncatalyzed reactions of O(2) (S = 1) with organic substrates (S = 0) are thermodynamically favorable but kinetically slow because they are spin-forbidden and the one-electron reduction potential of O(2) is unfavorable. In nature, many of these important O(2) reactions are catalyzed by metalloenzymes. In the case ...

    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.0704191104

    authors: Pau MY,Lipscomb JD,Solomon EI

    更新日期:2007-11-20 00:00:00

  • Native topology determines force-induced unfolding pathways in globular proteins.

    abstract::Single-molecule manipulation techniques reveal that stretching unravels individually folded domains in the muscle protein titin and the extracellular matrix protein tenascin. These elastic proteins contain tandem repeats of folded domains with beta-sandwich architecture. Herein, we propose by stretching two model sequ...

    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.97.13.7254

    authors: Klimov DK,Thirumalai D

    更新日期:2000-06-20 00:00:00

  • A second wave of Sonic hedgehog expression during the development of the bat limb.

    abstract::Sonic hedgehog (Shh) plays an integral role in both the anterior-posterior (A-P) patterning and expansion of developing vertebrate limbs through a feedback loop involving Fgfs, Bmps, and Gremlin. In bat limbs A-P patterning and the size of the digital field are unique. The posterior digits of the forelimb are elongate...

    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.0805308105

    authors: Hockman D,Cretekos CJ,Mason MK,Behringer RR,Jacobs DS,Illing N

    更新日期:2008-11-04 00:00:00

  • Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.

    abstract::Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes. TDP1 can also hydrolyze other 3'-end DNA alterations including 3'-phosphoglycolate and 3'-abasic sites, and ex...

    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.1009814107

    authors: Das BB,Dexheimer TS,Maddali K,Pommier Y

    更新日期:2010-11-16 00:00:00

  • Optimal decision making and matching are tied through diminishing returns.

    abstract::How individuals make decisions has been a matter of long-standing debate among economists and researchers in the life sciences. In economics, subjects are viewed as optimal decision makers who maximize their overall reward income. This framework has been widely influential, but requires a complete knowledge of the rew...

    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.1703440114

    authors: Kubanek J

    更新日期:2017-08-08 00:00:00

  • A strategy for the generation of conditional mutations by protein destabilization.

    abstract::Conditional mutations such as temperature-sensitive (ts) mutations are important for the analysis of protein function but are often difficult, or impossible, to obtain. Here we present a simple method for generating conditional mutations based on the use of a protein-destabilizing genetic element in combination with s...

    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.89.4.1249

    authors: Park EC,Finley D,Szostak JW

    更新日期:1992-02-15 00:00:00

  • mRNAs encoding ribulose-1,5-bisphosphate carboxylase remain bound to polysomes but are not translated in amaranth seedlings transferred to darkness.

    abstract::When light-grown seedlings of amaranth are transferred to total darkness, synthesis of the large subunit (LS) and small subunit (SS) of ribulose-1,5-bisphosphate carboxylase [RbuP(2)Case; 3-phospho-D-glycerate carboxylase (dimerizing), EC 4.1.1.39] is rapidly depressed. This reduction in RbuP(2)Case synthesis occurs i...

    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.85.12.4190

    authors: Berry JO,Carr JP,Klessig DF

    更新日期:1988-06-01 00:00:00

  • Regulation of N-methyl-D-aspartate-induced toxicity in the neostriatum: a role for metabotropic glutamate receptors?

    abstract::Glutamate release activates multiple receptors that interact with each other and thus determine the response of the cell. Exploring these interactions is critical to developing an understanding of the functional consequences of synaptic transmission. Activation of metabotropic glutamate receptors (mGluRs) inhibits N-m...

    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.93.3.1200

    authors: Colwell CS,Altemus KL,Cepeda C,Levine MS

    更新日期:1996-02-06 00:00:00

  • Peptide- and proton-driven allosteric clamps catalyze anthrax toxin translocation across membranes.

    abstract::Anthrax toxin is an intracellularly acting toxin in which sufficient information is available regarding the structure of its transmembrane channel, allowing for detailed investigation of models of translocation. Anthrax toxin, comprising three proteins-protective antigen (PA), lethal factor (LF), and edema factor-tran...

    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.1600624113

    authors: Das D,Krantz BA

    更新日期:2016-08-23 00:00:00

  • Role of gender, season, and familiarity in discrimination of conspecific song by zebra finches (Taeniopygia guttata).

    abstract::Operant conditioning techniques were used to assess how gender and song familiarity affect song discrimination in adult zebra finches (Taeniopygia guttata). Twenty-five males and females, divided into five cohorts, were trained to discriminate between conspecific songs at different times of year. Males discriminating ...

    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.89.4.1368

    authors: Cynx J,Nottebohm F

    更新日期:1992-02-15 00:00:00

  • Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.

    abstract::The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA inter...

    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.1803530115

    authors: Puno MR,Lima CD

    更新日期:2018-06-12 00:00:00

  • Exploiting the determinants of stochastic gene expression in Saccharomyces cerevisiae for genome-wide prediction of expression noise.

    abstract::Gene regulation is a process with many steps allowing for stochastic biochemical reactions, which leads to expression noise-i.e., the cell-to-cell stochastic fluctuation in protein abundance. Such expression noise can give rise to drastically diverse phenotypes, even within isogenic cell populations. Although numerous...

    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.0914302107

    authors: Li J,Min R,Vizeacoumar FJ,Jin K,Xin X,Zhang Z

    更新日期:2010-06-08 00:00:00

  • An archaeal primase functions as a nanoscale caliper to define primer length.

    abstract::The cellular replicative DNA polymerases cannot initiate DNA synthesis without a priming 3' OH. During DNA replication, this is supplied in the context of a short RNA primer molecule synthesized by DNA primase. The primase of archaea and eukaryotes, despite having varying subunit compositions, share sequence and struc...

    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.1806351115

    authors: Yan J,Holzer S,Pellegrini L,Bell SD

    更新日期:2018-06-26 00:00:00

  • Synchronous extinction of North America's Pleistocene mammals.

    abstract::The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (approximately 13,800-11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 ...

    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.0908153106

    authors: Faith JT,Surovell TA

    更新日期:2009-12-08 00:00:00

  • Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA.

    abstract::In the replication of human immunodeficiency virus type 1 (HIV-1), gag MA (matrix), a major structural protein of the virus, carries out opposing targeting functions. During virus assembly, gag MA is cotranslationally myristoylated, a modification required for membrane targeting of gag polyproteins. During virus infec...

    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.93.1.367

    authors: Bukrinskaya AG,Ghorpade A,Heinzinger NK,Smithgall TE,Lewis RE,Stevenson M

    更新日期:1996-01-09 00:00:00

  • Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

    abstract::Epithelial cells are organized into either a single layer (simple epithelia) or multiple layers (stratified epithelia). Maintenance of these cellular organizations requires distinct adhesive mechanisms involving many cell surface molecules. One such molecule is a cell surface proteoglycan, named syndecan, that contain...

    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.85.24.9562

    authors: Sanderson RD,Bernfield M

    更新日期:1988-12-01 00:00:00

  • Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis.

    abstract::Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2...

    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.1108220109

    authors: Sebastián D,Hernández-Alvarez MI,Segalés J,Sorianello E,Muñoz JP,Sala D,Waget A,Liesa M,Paz JC,Gopalacharyulu P,Orešič M,Pich S,Burcelin R,Palacín M,Zorzano A

    更新日期:2012-04-03 00:00:00

  • Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract.

    abstract::Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell...

    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.0808987105

    authors: Cooper MA,Son AI,Komlos D,Sun Y,Kleiman NJ,Zhou R

    更新日期:2008-10-28 00:00:00

  • Recent assembly of the Cerrado, a neotropical plant diversity hotspot, by in situ evolution of adaptations to fire.

    abstract::The relative importance of local ecological and larger-scale historical processes in causing differences in species richness across the globe remains keenly debated. To gain insight into these questions, we investigated the assembly of plant diversity in the Cerrado in South America, the world's most species-rich trop...

    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.0903410106

    authors: Simon MF,Grether R,de Queiroz LP,Skema C,Pennington RT,Hughes CE

    更新日期:2009-12-01 00:00:00

  • Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques.

    abstract::An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mut...

    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.2022496118

    authors: Murakowski DK,Barton JP,Peter L,Chandrashekar A,Bondzie E,Gao A,Barouch DH,Chakraborty AK

    更新日期:2021-02-02 00:00:00

  • An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma.

    abstract::Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide ...

    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.1610921114

    authors: Gujar AD,Le S,Mao DD,Dadey DY,Turski A,Sasaki Y,Aum D,Luo J,Dahiya S,Yuan L,Rich KM,Milbrandt J,Hallahan DE,Yano H,Tran DD,Kim AH

    更新日期:2016-12-20 00:00:00

  • On the promotion of human flourishing.

    abstract::Many empirical studies throughout the social and biomedical sciences focus only on very narrow outcomes such as income, or a single specific disease state, or a measure of positive affect. Human well-being or flourishing, however, consists in a much broader range of states and outcomes, certainly including mental and ...

    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.1702996114

    authors: VanderWeele TJ

    更新日期:2017-08-01 00:00:00

  • Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.

    abstract::Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl tripeptid...

    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.0407856101

    authors: Guan R,Roychowdhury A,Ember B,Kumar S,Boons GJ,Mariuzza RA

    更新日期:2004-12-07 00:00:00

  • CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency.

    abstract::Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ(9)-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid recept...

    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.1503395112

    authors: Smoum R,Baraghithy S,Chourasia M,Breuer A,Mussai N,Attar-Namdar M,Kogan NM,Raphael B,Bolognini D,Cascio MG,Marini P,Pertwee RG,Shurki A,Mechoulam R,Bab I

    更新日期:2015-07-14 00:00:00