scholarly journals The isoleucic acid triad: distinct impacts on plant defense, root growth, and formation of reactive oxygen species

2020 ◽  
Vol 71 (14) ◽  
pp. 4258-4270 ◽  
Author(s):  
Sibylle Bauer ◽  
Dereje W Mekonnen ◽  
Birgit Geist ◽  
Birgit Lange ◽  
Andrea Ghirardo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Root Growth ◽  
Pathogen Resistance ◽  
Inhibitory Effect ◽  
Marker Genes ◽  
Dependent Manner ◽  
In Planta ◽  
Tetrazolium Staining ◽  
Inhibit Root Growth ◽  
Branched Chain

Abstract Isoleucic acid (ILA), a branched-chain amino acid-related 2-hydroxycarboxylic acid, occurs ubiquitously in plants. It enhances pathogen resistance and inhibits root growth of Arabidopsis. The salicylic acid (SA) glucosyltransferase UGT76B1 is able to conjugate ILA. Here, we investigate the role of ILA in planta in Arabidopsis and reveal a triad of distinct responses to this small molecule. ILA synergistically co-operates with SA to activate SA-responsive gene expression and resistance in a UGT76B1-dependent manner in agreement with the observed competitive ILA-dependent repression of SA glucosylation by UGT76B1. However, ILA also shows an SA-independent stress response. Nitroblue tetrazolium staining and pharmacological experiments indicate that ILA induces superoxide formation of the wild type and of an SA-deficient (NahG sid2) line. In contrast, the inhibitory effect of ILA on root growth is independent of both SA and superoxide induction. These effects of ILA are specific and distinct from its isomeric compound leucic acid and from the amino acid isoleucine. Leucic acid and isoleucine do not induce expression of defense marker genes or superoxide production, whereas both compounds inhibit root growth. All three responses to ILA are also observed in Brassica napus.

scholarly journals Inhibitory Effect of Aroma on the Bitterness of Branched-Chain Amino Acid Solutions

2007 ◽  
Vol 55 (11) ◽  
pp. 1581-1584 ◽  
Author(s):  
Junji Mukai ◽  
Emi Tokuyama ◽  
Toshihiko Ishizaka ◽  
Sachie Okada ◽  
Takahiro Uchida
Keyword(s):  
Amino Acid ◽  
Inhibitory Effect ◽  
Acid Solutions ◽  
Branched Chain Amino Acid ◽  
Amino Acid Solutions ◽  
Branched Chain

scholarly journals Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated glucose transport in skeletal muscle cells in a BCAT2-dependent manner

2016 ◽  
Vol 311 (3) ◽  
pp. C518-C527 ◽  
Author(s):  
Mahshid Moghei ◽  
Pegah Tavajohi-Fini ◽  
Brendan Beatty ◽  
Olasunkanmi A. J. Adegoke
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Amino Acids ◽  
Glucose Transport ◽  
Direct Effect ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Positive Effects ◽  
Mtorc1 Signaling ◽  
Branched Chain

Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport ( P < 0.05). Importantly, we also showed that α-ketoisocaproic acid (KIC), an obligatory metabolite of leucine, stimulated mTORC1 signaling but suppressed insulin-stimulated glucose transport (−34%, P < 0.05) in an mTORC1-dependent manner. The effect of KIC on insulin-stimulated glucose transport was abrogated in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that catalyzes the reversible transamination of KIC to leucine. We conclude that although KIC can modulate muscle glucose metabolism, this effect is likely a result of its transamination back to leucine. Therefore, limiting the availability of leucine, rather than those of its metabolites, to skeletal muscle may be more critical in the management of insulin resistance and its sequelae.

scholarly journals HBV Pre-S1-Derived Myristoylated Peptide (Myr47): Identification of the Inhibitory Activity on the Cellular Uptake of Lipid Nanoparticles

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 929
Author(s):  
Masaya Nanahara ◽  
Ya-Ting Chang ◽  
Masaharu Somiya ◽  
Shun’ichi Kuroda
Keyword(s):  
Amino Acid ◽  
Cellular Uptake ◽  
Inhibitory Activity ◽  
Sodium Taurocholate ◽  
Lipid Nanoparticles ◽  
Inhibitory Effect ◽  
Amino Acid Sequences ◽  
Hbv Infection ◽  
Dependent Manner ◽  
Independent Manner

The Myr47 lipopeptide, consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2–48 peptide), is an effective commercialized anti-HBV drug that prevents the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, an activity which requires both N-myristoylation residue and specific amino acid sequences. We recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression. In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner and an amino acid sequence-independent manner, not only in human liver-derived cells but also in human non-liver-derived cells. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, lipopeptides are generally anchored by inserting their myristoyl residue into the lipid bilayer and can inhibit the interaction of LPs/HBsAg with apolipoprotein, thereby reducing the cellular uptake of LPs/HBsAg. Similarly, Myr47 would interact with HBV, inhibiting the uptake of HBV into human hepatic cells, while the inhibitory effect of Myr47 may be secondary to its ability to protect against HBV infection.

Insulin-mimetic agents vanadate and pervanadate stimulate glucose but inhibit amino acid uptake

1997 ◽  
Vol 272 (1) ◽  
pp. C156-C162 ◽  
Author(s):  
E. Tsiani ◽  
N. Abdullah ◽  
I. G. Fantus
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Tyrosine Phosphatase ◽  
Amino Acid Uptake ◽  
Inhibitory Effect ◽  
Acid Uptake ◽  
Dependent Manner ◽  
Transport Capacity ◽  
Insulin Mimetic ◽  
Biologic Effects

The protein tyrosine phosphatase (PTP) inhibitors vanadate and pervanadate (pV) exert insulin-like biologic effects. In cultured differentiated rat L6 skeletal muscle cells, vanadate and pV stimulated 2-deoxy-D-[3H]glucose uptake in a dose- and time-dependent manner. There was no increase in maximum stimulation by additional insulin. In contrast, whereas insulin stimulated [14C]methylaminoisobutyric acid (MeAIB) uptake, basal uptake was inhibited by vanadate and pV. Insulin-stimulated MeAIB uptake was also inhibited in a dose-dependent manner and completely abolished by 5 mM vanadate or 0.1 mM pV. The inhibitory effect on basal MeAIB uptake was associated with a decrease in transporter affinity and a small decrease in maximum transport capacity, whereas the insulin-stimulated increase in maximum transport capacity was completely inhibited. Inhibition of MeAIB uptake by vanadate and pV was not blocked by cycloheximide, and oubain did not inhibit uptake. Vanadate also inhibited amino acid deprivation-stimulated MeAIB uptake. Insulin-stimulated MeAIB uptake was also inhibited in rat hepatoma cells. Thus vanadate and pV mimic insulin to stimulate glucose uptake but inhibit system A amino acid uptake. The relative inhibitory concentrations of vanadate and pV suggest that the mechanism may involve PTP inhibition.

scholarly journals The metabolism of 4-methyl-2-oxopentanoate in rat pancreatic islets

1979 ◽  
Vol 184 (2) ◽  
pp. 291-301 ◽  
Author(s):  
J C Hutton ◽  
A Sener ◽  
W J Malaisse
Keyword(s):  
Amino Acid ◽  
Pancreatic Islets ◽  
Dependent Manner ◽  
Biosynthetic Activity ◽  
Isolated Pancreatic Islets ◽  
Branched Chain Amino Acid ◽  
Islet Tissue ◽  
Glutamate Dehydrogenase Activity ◽  
14Co2 Production ◽  
Branched Chain

1. Radioactively labelled 4-methyl-2-oxopentanoate was taken up by isolated pancreatic islets in a concentration- and pH-dependent manner and led to the intracellular accumulation of labelled amino acid and to a decrease in the intracellular pH. Uptake of 4-methyl-2-oxopentanoate did not appear to be either electrogenic or Na+-dependent. The islet content of 2-oxo acid radioactivity was not affected by either 2-cyano-3-hydroxy-cinnamate (10mM) or pyruvate (10mM), although both these substances inhibited the oxidation of [U-14C]4-methyl-2-oxopentanoate by islet tissue. 2. 4-Methyl-2-oxopentanoate markedly stimulated islet-cell respiration, ketone-body formation and biosynthetic activity. The metabolism of endogenous nutrients by islets appeared to be little affected by the compound. 3. Studies with the 3H- and 14C-labelled substrate revealed that 4-methyl-2-oxopentanoate was incorporated by islets into CO2, water, acetoacetate, L-leucine and to a lesser extent into islet protein and lipid. Carbon atoms C-2, C-3 and C-4 of the acetoacetate produced were derived from the carbon skeleton of the 4-methyl-2-oxopentanoate, but the acetoacetate carboxy group was derived from the incorporation of CO2. These results, and consideration of the relative rates of 14CO2 and acetoacetate formation from 1-14C-labelled as opposed to U-14C-labelled 4-methyl-2-oxopentanoate, led to the conclusion that the pathway of catabolism of this 2-oxo acid in pancreatic islets is identical with that described in other tissues. The amination of 4-methyl-2-oxopentanoate by islets was attributed to the presence of a branched-chain amino acid aminotransferase (EC 2.6.1.42) activity in the tissue. Although glutamate dehydrogenase activity was demonstrated in islet tissue, the reductive amination of 2-oxoacids did not seem to be of importance in the formation of leucine from 4-methyl-2-oxopentanoate. 4. The results of experiments with respiratory inhibitors and uncouplers, and the finding that 14CO2 production and islet respiration were linked in a 1:1 stoicheiometry suggested that 4-methyl-2-oxopentanoate catabolism was coupled to mitochondrial oxidative phosphorylation. The catabolism of 4-methyl-2-oxopentanoate in islet tissue appeared to be regulated at the level of the initial 2-oxo acid dehydrogenase (EC 1.2.1.25) reaction.

scholarly journals ERF-VII transcription factors induce ethanol fermentation in response to amino acid biosynthesis-inhibiting herbicides

2019 ◽  
Vol 70 (20) ◽  
pp. 5839-5851 ◽  
Author(s):  
Miriam Gil-Monreal ◽  
Beatrice Giuntoli ◽  
Ana Zabalza ◽  
Francesco Licausi ◽  
Mercedes Royuela
Keyword(s):  
Amino Acid ◽  
Ethanol Fermentation ◽  
Herbicide Tolerance ◽  
Amino Acid Biosynthesis ◽  
Dependent Manner ◽  
Low Oxygen ◽  
Acid Biosynthesis ◽  
Response Factors ◽  
Oxygen Conditions ◽  
Branched Chain

Abstract Herbicides inhibiting either aromatic or branched-chain amino acid biosynthesis trigger similar physiological responses in plants, despite their different mechanism of action. Both types of herbicides are known to activate ethanol fermentation by inducing the expression of fermentative genes; however, the mechanism of such transcriptional regulation has not been investigated so far. In plants exposed to low-oxygen conditions, ethanol fermentation is transcriptionally controlled by the ethylene response factors-VII (ERF-VIIs), whose stability is controlled in an oxygen-dependent manner by the Cys-Arg branch of the N-degron pathway. In this study, we investigated the role of ERF-VIIs in the regulation of the ethanol fermentation pathway in herbicide-treated Arabidopsis plants grown under aerobic conditions. Our results demonstrate that these transcriptional regulators are stabilized in response to herbicide treatment and are required for ethanol fermentation in these conditions. We also observed that mutants with reduced fermentative potential exhibit higher sensitivity to herbicide treatments, thus revealing the existence of a mechanism that mimics oxygen deprivation to activate metabolic pathways that enhance herbicide tolerance. We speculate that this signaling pathway may represent a potential target in agriculture to affect tolerance to herbicides that inhibit amino acid biosynthesis.

scholarly journals BrnQ-type Branched-chain Amino Acid Transporters Influence Bacillus anthracis Growth and Virulence

2021 ◽  
Author(s):  
Soumita Dutta ◽  
Ileana D Corsi ◽  
Naomi Bier ◽  
Theresa M Koehler
Keyword(s):  
Amino Acid ◽  
Bacillus Anthracis ◽  
Murine Model ◽  
Amino Acid Transporters ◽  
Dependent Manner ◽  
Isoleucine Leucine ◽  
Virulence Gene Expression ◽  
Branched Chain Amino Acid ◽  
Branched Chain

Bacillus anthracis, the anthrax agent, exhibits robust proliferation in diverse niches of mammalian hosts. Metabolic attributes of B. anthracis that permit rapid growth in multiple mammalian tissues have not been established. We posit that branched-chain amino acid (BCAA: Isoleucine, leucine and valine) metabolism is key to B. anthracis pathogenesis. Increasing evidence indicates relationships between B. anthracis virulence and expression of BCAA-related genes. Expression of some BCAA-related genes is altered during culture in bovine blood in vitro and the bacterium exhibits valine auxotrophy in a blood serum mimic medium. Transcriptome analyses have revealed that the virulence regulator AtxA, that positively affects expression of the anthrax toxin and capsule genes, negatively regulates genes predicted to be associated with BCAA biosynthesis and transport. Here, we show that B. anthracis growth in defined media is severely restricted in the absence of exogenous BCAAs, indicating that BCAA transport is required for optimal growth in vitro. We demonstrate functional redundancy among multiple BrnQ-type BCAA transporters. Three transporters are associated with isoleucine and valine transport, and deletion of one, BrnQ3, attenuates virulence in a murine model for anthrax. Interestingly, an ilvD-null mutant lacking dihydroxy-acid dehydratase, an enzyme essential for BCAAs synthesis, exhibits unperturbed growth when cultured in media containing BCAAs, but is highly attenuated in the murine model. Finally, our data show that BCAAs enhance AtxA activity in a dose-dependent manner, suggesting a model in which BCAAs serve as a signal for virulence gene expression.

scholarly journals Branched-chain amino acid interactions in growing pig diets1

2019 ◽  
Vol 3 (4) ◽  
pp. 1246-1253 ◽  
Author(s):  
Henrique S Cemin ◽  
Mike D Tokach ◽  
Jason C Woodworth ◽  
Steve S Dritz ◽  
Joel M DeRouchey ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Growth Performance ◽  
Feed Intake ◽  
Negative Impact ◽  
Amino Acid Profile ◽  
Inhibitory Effect ◽  
Keto Acid ◽  
Branched Chain ◽  
The Impact

Abstract The branched-chain amino acids (BCAA) Leu, Ile, and Val share the first steps of their catabolism due to similarities in their structure. The BCAA are reversibly transaminated in skeletal muscle through the activity of branched-chain aminotransferase and then transported to the liver. They undergo an irreversible decarboxylation catalyzed by the branched-chain α-keto acid dehydrogenase complex. Both enzymes are common to Leu, Ile, and Val and increased enzymatic activity stimulated by an excess of one of them will increase the catabolism of all BCAA, which can result in antagonisms. Leucine and its keto acid are the most potent stimulators of BCAA catabolic enzymes. Moreover, BCAA and large neutral amino acids (LNAA) share common brain transporters. Research has shown that high concentrations of BCAA, especially Leu, can decrease the absorption of LNAA, such as Trp, which is a precursor of serotonin and can have a significant impact in feed intake regulation. Finally, high Leu concentrations have the ability to overstimulate the mTOR signaling pathway, resulting in an inhibitory effect on feed intake. Most of the research conducted to evaluate the impact of BCAA on growth performance of pigs seems to agree that high levels of Leu decrease weight gain, mostly due to a reduction in feed intake. However, some studies, mostly with finishing pigs, observed no evidence for an impact on growth performance even with extremely high levels of Leu. It could be hypothesized that these inconsistencies are driven by the entire dietary amino acid profile as opposed to only considering the level of Leu. Grow-finish diets typically contain high levels of Leu, but the other BCAA are also well above the requirement and could potentially mitigate the negative impact of Leu on BCAA catabolism. Indeed, some studies suggest that when diets contain high levels of Leu, more Ile and Val are needed to optimize growth performance. However, the precise relationship between BCAA and their balance in swine diets is not fully understood. More research is needed to understand and quantify the relationship between LNAA and BCAA.

Effects of amino acid neurotransmitters on spontaneous muscular activity of the rumen amphistome, Gastrothylax crumenifer

2009 ◽  
Vol 83 (4) ◽  
pp. 385-389 ◽  
Author(s):  
P.K. Verma ◽  
D. Kumar ◽  
S.K. Tandan
Keyword(s):  
Amino Acid ◽  
Muscular Activity ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Helminth Parasites ◽  
Gamma Aminobutyric Acid ◽  
Amino Acid Neurotransmitters ◽  
Concentration Dependent Manner ◽  
Gastrothylax Crumenifer ◽  
Spontaneous Contractions

AbstractAmino acid neurotransmitters play an important role in regulating neuromuscular activity of helminth parasites. The present study aimed to investigate the effects of different amino acid neurotransmitters [l-glutamate, glycine, gamma-aminobutyric acid (GABA)] on spontaneous muscular activity of isometrically mounted Gastrothylax crumenifer. l-Glutamate caused a significant increase in the amplitude and frequency of spontaneous contractions of rumen fluke at 10− 7–10− 4 m and at 10− 5–10− 4 m concentrations, respectively. Glycine application (10− 7–10− 3 m) produced a significant decrease in the amplitude and frequency of spontaneous muscular contractions in a concentration-dependent manner, as compared to control amplitude (0.53 ± 0.02 g) and frequency (51 ± 4.65/5 min). Similarly, GABA produced a significant (P < 0.05) decrease in amplitude, baseline tension and frequency of spontaneous muscular contractions of G. crumenifer. To further substantiate the GABA effect, GABAA receptor antagonists, picrotoxin and bicuculline were applied. Picrotoxin (10− 5–10− 3 m) caused a significant (P < 0.05) increase in amplitude, baseline tension and frequency of the rumen fluke as compared to control; whereas bicuculline did not elicit any observable effect in these attributes in isometrically mounted rumen flukes. These observations suggested that l-glutamate has an excitatory, whereas GABA and glycine have an inhibitory, effect on the spontaneous muscular activity of G. crumenifer.

scholarly journals The miR-200b-3p/ERG/PTHrP Axis Mediates the Inhibitory Effect of Ethanol on the Differentiation of Rat Fetal Chondrocytes into Articular Cartilage

2021 ◽  
Author(s):  
Qubo Ni ◽  
Haitao Chen ◽  
Bin Li ◽  
Hangyuan He ◽  
Huasong Shi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inhibitory Effect ◽  
Ethanol Exposure ◽  
Luciferase Reporter ◽  
Marker Genes ◽  
Dependent Manner ◽  
Prenatal Ethanol Exposure ◽  
Concentration Dependent Manner ◽  
Marrow Mesenchymal Stem Cells

Abstract Background This study aims to further explore cartilage development in prenatal ethanol exposure (PEE) offspring at different times to explore the specific time points and mechanism of ethanol-induced fetal cartilage dysplasia. Methods On gestational day (GD)14, GD17, and GD20, PEE fetal cartilage was evaluated by morphological analysis. RT-qPCR, immunohistochemistry, and immunofluorescence were used to detect the expression of cartilage marker genes and their regulatory factors. Bone marrow mesenchymal stem cells (BMSCs) were used to explore the effect of ethanol on the differentiation of chondrocytes. Additionally, we used inhibitors, overexpression plasmids and a luciferase reporter assay on GD17 chondrocytes to verify the mechanism. Findings: PEE significantly reduced cartilage matrix content and the expression of marker genes on GD17 and GD20 but had no effect on GD14. The inhibition of chondrogenic differentiation by PEE mainly occurred on GD14-17. Furthermore, the expression of miR-200b-3p was increased, while that of ERG and PTHrP was markedly reduced in PEE fetal cartilage. In vitro, ethanol (30–120 mM) inhibited the differentiation of BMSCs into chondrocytes in a concentration-dependent manner, accompanied by strong expression of miR-200b-3p and low expression of ERG and PTHrP. Moreover, PTHLH and ERG overexpressed, as well as a miR-200b-3p inhibitor reversed the inhibitory effect of ethanol on the differentiation of fetal chondrocytes. Furthermore, miR-200b-3p could target and negatively regulate ERG. Interpretation: PEE can significantly inhibit the development of articular cartilage, especially during articular cartilage formation. The mechanism is related to the decreased differentiation of fetal cartilage into articular cartilage mediated by the miR-200b-3p/ERG/PTHrP axis.

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