Chronic activation of mTOR complex 1 by branched chain amino acids and organ hypertrophy.

Abstract:

:The mitochondrial branched chain aminotransferase-deficient mouse model (BCATm KO), which exhibits elevated plasma and tissue branched chain amino acids (BCAAs), was used to study the effect of BCAAs on mammalian target of rapamycin complex 1 (mTORC1) regulation of organ size. BCATm is the first enzyme in the BCAA catabolic pathway. BCATm KO mouse exhibited hypertrophy of heart, kidneys, and spleen. On the other hand, the mass of the gastrocnemius was reduced relative to body mass. Feeding the mice with a diet supplemented with rapamycin prevented the enlargement of the heart and spleen, suggesting that mTORC1 is the mediator of these effects. Consistently, enlargement of these organs was accompanied by the activation of mTORC1 complex as evidenced by enhanced levels of S6 and 4E-BP1 phosphorylation. HSP20, HSP27 and GAPDH were also increased in the heart but not gastrocnemius, consistent with mTORC1 activation. Liver, however, displayed no weight difference between the KO and the wild-type mice despite the highest activation level of mTORC1 complex. These observations suggest that the anabolic effect of mTORC1 activation at the organ level by BCAAs and inhibition by rapamycin are complex phenomenon and tissue-specific. In addition, it suggests that rapamycin can be used to counter hypertrophy of the organs when activation of mTORC1 is the underlying cause.

journal_name

Amino Acids

journal_title

Amino acids

authors

Neishabouri SH,Hutson SM,Davoodi J

doi

10.1007/s00726-015-1944-y

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1167-82

issue

6

eissn

0939-4451

issn

1438-2199

journal_volume

47

pub_type

杂志文章
  • Functional significance of eIF5A and its hypusine modification in eukaryotes.

    abstract::The unusual basic amino acid, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)-lysine], is a modified lysine with the addition of the 4-aminobutyl moiety from the polyamine spermidine. This naturally occurring amino acid is a product of a unique posttranslational modification that occurs in only one cellular protein, euk...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-009-0408-7

    authors: Park MH,Nishimura K,Zanelli CF,Valentini SR

    更新日期:2010-02-01 00:00:00

  • Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

    abstract::Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailabili...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-017-2471-9

    authors: Wester A,Devocelle M,Tallant EA,Chappell MC,Gallagher PE,Paradisi F

    更新日期:2017-10-01 00:00:00

  • Effects of phenylalanine and phenylpyruvate on ATP-ADP hydrolysis by rat blood serum.

    abstract::The nucleotide (ATP-ADP)/nucleoside (adenosine) ratio in the circulation can modulate the processes of vasoconstriction, vasodilatation and platelet aggregation. The main objective of the present study with rat blood serum was to evaluate the possibility of changes in nucleotide hydrolysis by phenylalanine (Phe) and p...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-002-0345-1

    authors: Rücker B,Oses JP,Kirst IB,Berti SL,Bonan CD,Battastini AM,Sarkis JJ

    更新日期:2003-06-01 00:00:00

  • L-Tryptophan: Biochemical, nutritional and pharmacological aspects.

    abstract::Tryptophan is important both for protein synthesis and as a precursor of niacin, serotonin and other metabolites. Tryptophan is an unusual amino acid because of the complexity of its metabolism, the variety and importance of its metabolites, the number and diversity of the diseases it is involved in, and because of it...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/BF00806091

    authors: Sainio EL,Pulkki K,Young SN

    更新日期:1996-03-01 00:00:00

  • Prediction of mitochondrial proteins based on genetic algorithm - partial least squares and support vector machine.

    abstract::Mitochondria are essential cell organelles of eukaryotes. Hence, it is vitally important to develop an automated and reliable method for timely identification of novel mitochondrial proteins. In this study, mitochondrial proteins were encoded by dipeptide composition technology; then, the genetic algorithm-partial lea...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-006-0465-0

    authors: Tan F,Feng X,Fang Z,Li M,Guo Y,Jiang L

    更新日期:2007-11-01 00:00:00

  • A hypothesis on the biochemical mechanism of BH(4)-responsiveness in phenylalanine hydroxylase deficiency.

    abstract::We describe six children with tetrahydrobiopterin (BH(4)) responsive phenylalanine hydroxylase (PAH) deficiency. All patients carry two mutant alleles in the PAH gene. Cofactor deficiency was excluded. The effect of BH(4) administration was studied by correlating different oral BH(4) doses with plasma phenylalanine le...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-002-0354-0

    authors: Steinfeld R,Kohlschütter A,Ullrich K,Lukacs Z

    更新日期:2003-07-01 00:00:00

  • Mapping surface residues of eIF5A that are important for binding to the ribosome using alanine scanning mutagenesis.

    abstract::The translation elongation factor eIF5A is conserved through evolution and is necessary to rescue the ribosome during translation elongation of polyproline-containing proteins. Although the site of eIF5A binding to the ribosome is known, no systematic analysis has been performed so far to determine the important resid...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-016-2279-z

    authors: Barbosa NM,Boldrin PE,Rossi D,Yamamoto PA,Watanabe TF,Serrão VH,Hershey JW,Fraser CS,Valentini SR,Zanelli CF

    更新日期:2016-10-01 00:00:00

  • Role of neuronal nitric oxide synthase in the regulation of the neuroendocrine stress response in rodents: insights from mutant mice.

    abstract::Nitric oxide (NO) is a free radical gas synthesised from arginine and oxygen by enzymes of the family of the nitric oxide synthase. In particular, the neuronal nitric oxide synthase (nNOS) is highly expressed by cells of the hypothalamic paraventricular nucleus, where the sympatho-adrenal system, the hypothalamic-pitu...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-007-0630-0

    authors: Orlando GF,Wolf G,Engelmann M

    更新日期:2008-06-01 00:00:00

  • L-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells.

    abstract::This study tested the hypothesis that L-arginine (Arg) may stimulate cell proliferation and prevent lipopolysaccharide (LPS)-induced death of intestinal cells. Intestinal porcine epithelial cells (IPEC-1) were cultured for 4 days in Arg-free Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 10, 100 or 3...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-009-0334-8

    authors: Tan B,Yin Y,Kong X,Li P,Li X,Gao H,Li X,Huang R,Wu G

    更新日期:2010-04-01 00:00:00

  • The designer leptin antagonist peptide Allo-aca compensates for short serum half-life with very tight binding to the receptor.

    abstract::The leptin receptor antagonist peptide Allo-aca exhibits picomolar activities in various cellular systems and sub-mg/kg subcutaneous efficacies in animal models making it a prime drug candidate and target validation tool. Here we identified the biochemical basis for its remarkable in vivo activity. Allo-aca decomposed...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-013-1650-6

    authors: Otvos L Jr,Vetter SW,Koladia M,Knappe D,Schmidt R,Ostorhazi E,Kovalszky I,Bionda N,Cudic P,Surmacz E,Wade JD,Hoffmann R

    更新日期:2014-04-01 00:00:00

  • Observations on the relationship between the extracellular changes of taurine and glutamate during cortical spreading depression, during ischemia, and within the area surrounding a thrombotic infarct.

    abstract::Taurine and glutamate were monitored by microdialysis technique during various cerebral insults: a. Application of K+ triggered a cortical spreading depression (CSD). Taurine and glutamate increased concomitantly but recovery of glutamate was faster than that of taurine. b. Application of NMDA induced also CSD but onl...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s007260070007

    authors: Scheller D,Szathmary S,Kolb J,Tegtmeier F

    更新日期:2000-01-01 00:00:00

  • Synthesis of the amino acid conjugates of epi-jasmonic acid.

    abstract::The TES ether of the C6-hydroxy derivative of naturally occurring epi-jasmonic acid (epi-JA) was designed as epimerization-free equivalent of epi-JA. The TES ether was synthesized from (1R,4S)-4-hydroxycyclopent-2-enyl acetate in 13 steps. The acid part of the ether was activated with ClCO2Bui and subjected to condens...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-011-0925-z

    authors: Ogawa N,Kobayashi Y

    更新日期:2012-05-01 00:00:00

  • Use ofα-aminoisobutyric acid and isovaline as marker amino acids for the detection of fungal polypeptide antibiotics. Screening ofHypocrea.

    abstract::Filamentous fungi of the genusHypocrea were grown on malt extract/peptone agar, the mycelia were extracted with dichloromethane/methanol, and the extracts were totally hydrolyzed with 6 N HCl (110°C, 24 h). The amino acids (AA) released from peptides were converted into theirN(O)-pen-tafluoropropionyl 1-propyl esters ...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/BF00806923

    authors: Brückner H,Maisch J,Reinecke C,Kimonyo A

    更新日期:1991-06-01 00:00:00

  • The inhibitory effect of various indolyl amino acid derivatives on arginase activity in macrophages.

    abstract::Numerous indolyl amino acids and their derivatives inhibited arginase activity. The inhibition was found to be non-competitive, - at least partly - allosteric, and independent on manganese ions in the active site, and it cannot be explained by the dissociation of arginase homotrimers. Indole alone is weakly inhibitory...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-006-0470-3

    authors: Hrabák A,Bajor T,Mészáros G

    更新日期:2008-02-01 00:00:00

  • Optimal and effective oral dose of taurine to prolong exercise performance in rat.

    abstract::The aim of this study was to determine the effective and optimum dose of taurine for exercise performance and to maintain tissue taurine concentration. Rats received a respective daily dose of 0, 20, 100, and 500 mg/kg body weight of taurine (EC and ET-1, -2, -3 groups, respectively) for two weeks, and then, were subj...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-004-0133-1

    authors: Miyazaki T,Matsuzaki Y,Ikegami T,Miyakawa S,Doy M,Tanaka N,Bouscarel B

    更新日期:2004-12-01 00:00:00

  • Effects of GABA-transaminase inhibitor Vigabatrin on thermoregulation in rats.

    abstract::Vigabatrin is a GABA derivative (gamma-vinyl GABA) which inhibits irreversibly the enzyme activity of GABA transaminase and thus increased indirectly brain GABA concentrations. We have used body temperature assay to examine the effects of Vigabatrin on thermoregulation in intact rats. In order to understand the mechan...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0754-5

    authors: Nikolov RP,Yakimova KS

    更新日期:2011-05-01 00:00:00

  • Some of the amino acid chemistry going on in the Laboratory of Amino Acids, Peptides and Proteins.

    abstract::Some of the chemistry of amino acids going on in our laboratory (Laboratoire des Amino acides Peptides et Protéines) is described as well as some mass spectrometry methodology for their characterization particularly on solid supports. Several aspects are presented including: (i) the stereoselective synthesis of natura...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/BF01388176

    authors: Bouifraden S,Drouot C,el Hadrami M,Guenoun F,Lecointe L,Mai N,Paris M,Pothion C,Sadoune M,Sauvagnat B,Amblard M,Aubagnac JL,Calmes M,Chevallet P,Daunis J,Enjalbal C,Fehrentz JA,Lamaty F,Lavergne JP,Lazaro R,Rollan

    更新日期:1999-01-01 00:00:00

  • Proteomic analysis of apoptosis induction in human lung cancer cells by recombinant MVL.

    abstract::Lung cancer is still difficult to treat by current chemotherapeutic procedures. We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis viridis, also has antitumor activity. The objective of this study was to investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic chan...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0791-0

    authors: Li Y,Zhang B,Wang X,Yan H,Chen G,Zhang X

    更新日期:2011-10-01 00:00:00

  • Cancer therapy and prevention by green tea: role of ornithine decarboxylase.

    abstract::Green tea which is widely consumed in China, Japan and India, contains polyphenolic compounds, which account for 30% of the dry weight of the leaves. Most of the polyphenols are flavanols, of which (-)-epigallocatechin-3-gallate (EGCG) is most abundant. Epidemiological studies revealed that the incidences of stomach a...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s726-002-8197-9

    authors: Bachrach U,Wang YC

    更新日期:2002-01-01 00:00:00

  • Effect of glutamate and angiotensin II on whole cell currents and release of nitric oxide in the rat subfornical organ.

    abstract::Blood-borne angiotensin II (AngII) is known to mediate water-intake by its excitatory effect on neurons in the subfornical organ (SFO). Conversely, nitric oxide (NO) has exclusively inhibitory effects on rat SFO-neurons and on SFO-mediated water-intake. Extracellular and patch-clamp recordings from freshly dissociated...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/BF01345251

    authors: Schmid HA

    更新日期:1998-01-01 00:00:00

  • Enhanced osteoblast adhesion on transglutaminase 2-crosslinked fibronectin.

    abstract::Fibronectin (FN) is a cell adhesion protein that binds integrins in a process also involving the protein-crosslinking enzyme transglutaminase 2 (TG2) as a co-receptor. The cell-adhesive property of TG2 has been linked to a complex formation with FN and to its ability to crosslink and polymerize FN on the cell surface....

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-008-0125-7

    authors: Forsprecher J,Wang Z,Nelea V,Kaartinen MT

    更新日期:2009-04-01 00:00:00

  • Low-resolution structure, oligomerization and its role on the enzymatic activity of a sucrose-6-phosphate hydrolase from Bacillus licheniformis.

    abstract::Knowing the key features of the structure and the biochemistry of proteins is crucial to improving enzymes of industrial interest like β-fructofuranosidase. Gene sacA from Bacillus licheniformis ATCC 14580 codifies a sucrose-6-phosphate hydrolase, a β-fructofuranosidase (E.C. 3.1.2.26, protein BlsacA), which has no cr...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-018-02690-2

    authors: Mera A,de Lima MZT,Bernardes A,Garcia W,Muniz JRC

    更新日期:2019-04-01 00:00:00

  • Immunocytochemical study by two photon fluorescence microscopy of the distribution of GABA(A) receptor subunits in rat cerebellar granule cells in culture.

    abstract::An immunocytochemical investigation of the expression of alpha(1), alpha(6), beta(2/3), gamma(2) and delta subunits was performed on rat cerebellum granule cells in culture by the two photon microscopy technique. The first four subunits appear to be expressed abundantly in these cells, whereas the delta one seems to b...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-003-0006-z

    authors: Merlo F,Balduzzi R,Cupello A,Robello M

    更新日期:2004-02-01 00:00:00

  • A new method to synthesize creatine derivatives.

    abstract::Creatine is an amino acid that has a pivotal role in energy metabolism of cells. Creatine acts as an "ATP shuttle", carrying ATP to the sites where it is utilized, through its reversible phosphorylation by creatine kinase. Moreover, the creatine-phosphocreatine system delays ATP depletion during anoxia or ischemia, th...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-013-1525-x

    authors: Garbati P,Salis A,Adriano E,Galatini A,Damonte G,Balestrino M,Millo E

    更新日期:2013-10-01 00:00:00

  • Synthesis and characterization of aspartic acid complexes of antimony and bismuth triiodide.

    abstract::New bioinorganic complexes of the aspartic acid with the antimony or bismuth triiodide were synthesized by a direct solid-solid reaction at room temperature. The formula of the complex is MI(3)[OOCCH(2)CH(NH(2))CO](2.5) x 2.5H(2)O (M = Sb, Bi). The complex may be a dimer with bridge structure. The crystal structure of...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-005-0210-0

    authors: Jia RR,Wu CP,Wu S,Yang YX,Chen YR,Jia YQ

    更新日期:2006-07-01 00:00:00

  • Plasma free amino acid profiles and nutrition proteins in chronic renal failure; effect of dialysis treatment.

    abstract::A well preserved nutritional status is beneficial in chronically uremic patients for slowing the pace of deterioration of renal function, and delaying the need for dialysis therapy. The purpose of this study was to assess the nutritional profile of 10 patients in a steady state of advanced CRF, and of 15 patients with...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/BF00806083

    authors: Troupel S,Le Moel G,Bouten A,Fessi H,Boukhalfa Z,Stamatakis G,Lecon V,Mery J,Agneray J,Jacobs C

    更新日期:1992-02-01 00:00:00

  • Two piperazic acid-containing cyclic hexapeptides from Streptomyces alboflavus 313.

    abstract::Two novel cyclic hexapeptides, designated NW-G10 (1) and NW-G11 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their relative structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of several constituent amino acids were determined b...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-012-1303-1

    authors: Wei S,Fan L,Wu W,Ji Z

    更新日期:2012-11-01 00:00:00

  • SILAC-based proteomic analysis to dissect the "histone modification signature" of human breast cancer cells.

    abstract::In living cells, the N-terminal tails of core histones, the proteinaceous component of nucleosomes, are subjected to a range of covalent post-translational modifications (PTMs), which have specific roles in modulating chromatin structure and function. A growing body of evidence suggests that deregulation of histone mo...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-010-0668-2

    authors: Cuomo A,Moretti S,Minucci S,Bonaldi T

    更新日期:2011-07-01 00:00:00

  • Maillard reaction products in tissue proteins: new products and new perspectives.

    abstract::The chemical modification of protein by nonenzymatic browning or Maillard reactions increases with age and in disease. Maillard products are formed by reactions of both carbohydrate- and lipid-derived intermediates with proteins, leading to formation of advanced glycation and lipoxidation end-products (AGE/ALEs). Thes...

    journal_title:Amino acids

    pub_type: 杂志文章,评审

    doi:10.1007/s00726-003-0017-9

    authors: Thorpe SR,Baynes JW

    更新日期:2003-12-01 00:00:00

  • Identification and bioactivity evaluation of the first neuropeptide from the lesser-known insect order Embioptera (webspinner).

    abstract::A species of the poorly studied order Embioptera, the webspinner Oligotoma saundersii, is investigated for its complement of neuropeptides of the adipokinetic hormone (AKH) family. A methanolic extract of its corpora cardiaca (CC) is able to effect carbohydrate mobilization in the cockroach, Periplaneta americana, and...

    journal_title:Amino acids

    pub_type: 杂志文章

    doi:10.1007/s00726-016-2229-9

    authors: Gäde G,Šimek P,Marco HG

    更新日期:2016-07-01 00:00:00