Blastocyst trophectoderm endocytic activation, a marker of adverse developmental programming

The mouse preimplantation embryo is sensitive to its environment including maternal dietary protein restriction which can alter the developmental programme and affect lifetime health. Previously, we have shown maternal low protein diet (LPD) causes reduction in blastocyst mTORC1 signalling coinciding with reduced availability of branched-chain amino acids (BCAAs) in surrounding uterine fluid. BCAA deficiency leads to increased endocytosis and lysosome biogenesis in blastocyst trophectoderm (TE), a response to promote compensatory histotrophic nutrition. Here, we first investigated the induction mechanism by individual variation in BCAA deficiency in an in vitro quantitative model of TE responsiveness. We found isoleucine (ILE) deficiency as the most effective activator of TE endocytosis and lysosome biogenesis, with less potent roles for other BCAAs and insulin; cell volume was also influential. TE response to low ILE included upregulation of vesicles comprising megalin receptor and cathepsin-B and the response was activated from blastocyst formation. Second, we identified the transcription factor TFEB as mediating the histotrophic response by translocation from cytoplasm to nucleus during ILE deficiency and in response to mTORC1 inhibition. Lastly, we investigated whether a similar mechanism responsive to maternal nutritional status was found in human blastocysts. Blastocysts from women with high body-mass index, but not the method of fertilisation, revealed stimulated lysosome biogenesis and TFEB nuclear migration. We propose TE lysosomal phenotype as an early biomarker of environmental nutrient stress that may associate with long-term health outcome.

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Reversible ATP-induced inactivation of branched-chain 2-oxo acid dehydrogenase

Biochemical Journal ◽

10.1042/bj1920155 ◽

1980 ◽

Vol 192 (1) ◽

pp. 155-163 ◽

Cited By ~ 45

Author(s):

R Odessey

Keyword(s):

Skeletal Muscle ◽

Liver Mitochondria ◽

Initial Activity ◽

Rat Skeletal Muscle ◽

Kidney Mitochondria ◽

Physiological Conditions ◽

Acid Dehydrogenase ◽

Skeletal Muscle Mitochondria ◽

Branched Chain

The branched chain 2-oxo acid dehydrogenase from rat skeletal muscle, heart, kidney and liver mitochondria can undergo a reversible activation-inactivation cycle in vitro. Similar results were obtained with the enzyme from kidney mitochondria of pig and cow. The dehydrogenase is markedly inhibited by ATP and the inhibition is not reversed by removing the nucleotide. The non-metabolizable ATP analogue adenosine 5′-[beta gamma-imido] triphosphate can block the effect of ATP when added with the nucleotide, but has no effect by itself, nor can it reverse the inhibition in mitochondria preincubated with ATP. These findings suggest that the branched chain 2-oxo acid dehydrogenase undergoes a stable modification that requires the splitting of the ATP gamma-phosphate group. In skeletal muscle mitochondria the rate of inhibition by ATP is decreased by oxo acid substrates and enhanced by NADH. The dehydrogenase can be reactivated 10-20 fold by incubation at pH 7.8 in a buffer containing Mg2+ and cofactors. Reactivation is blocked by NaF (25 mM). The initial activity of dehydrogenase extracted from various tissues of fed rats varies considerably. Activity is near maximal in kidney and liver whereas the dehydrogenase in heart and skeletal muscle is almost completely inactivated. These studies emphasize that comparisons of branched chain 2-oxo acid dehydrogenase activity under various physiological conditions or in different tissues must take into account its state of activation. Thus the possibility exists that the branched chain 2-oxo acid dehydrogenase may be physiologically regulated via a covalent mechanism.

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The impact of long-term dietary pattern of fecal donor on in vitro fecal fermentation properties of inulin

Food & Function ◽

10.1039/c5fo00987a ◽

2016 ◽

Vol 7 (4) ◽

pp. 1805-1813 ◽

Cited By ~ 9

Author(s):

Junyi Yang ◽

Devin J. Rose

Keyword(s):

Fatty Acids ◽

Short Chain Fatty Acids ◽

Processed Meats ◽

Branched Chain Fatty Acids ◽

Fiber Plant ◽

Branched Chain ◽

The Impact ◽

Chain Fatty Acids

A diet high in whole grains, dry beans, and certain vegetables that contributed dietary fiber, plant protein, and B vitamins resulted in high short chain fatty acids, while a diet high in diary and processed meats that provided cholesterol and little fiber resulted in high branched chain fatty acids and ammonia during fecal fermentation of inulin.

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Branched chain amino Acids as in vitro and in vivo Anti-Oxidation Compounds

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00677 ◽

2021 ◽

pp. 3899-3904

Author(s):

Moath Alqaraleh ◽

Violet Kasabri ◽

Ibrahim Al-Majali ◽

Nihad Al-Othman ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Amino Acids ◽

Branched Chain Amino Acids ◽

Raw 264.7 ◽

Raw 264.7 Cell ◽

Branched Chain ◽

Raw 264.7 Cell Line

Background and aims: Branched chain amino acids (BCAAs) can be tightly connected to metabolism syndrome (MetS) which can be counted as a metabolic indicator in the case of insulin resistance (IR). The aim of this study was to assess the potential role of these acids under oxidative stress. Material and Methods: the in vitro antioxidant activity of BCAAs was assessed using free radical 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging assays. For further check, a qRT-PCR technique was madefor detection the extent of alterations in gene expression of antioxidative enzymes (catalase and glutathione peroxidase (Gpx)) in lipopolysaccharides (LPS(-induced macrophages RAW 264.7 cell line. Additionally, BCAAs antioxidant activity was evaluated based on plasma H2O2 levels and xanthine oxidase (XO) activity in prooxidative LPS-treated mice. Results: Different concentrations of BCAAs affected on DPPH radical scavenging activity but to lesser extent than the ascorbic acid. Besides, BCAAs obviously upregulated the gene expression levels of catalases and Gpx in LPS-modulated macrophage RAW 264.7 cell line. In vivo BCAAs significantly minimized the level of plasma H2O2 as well as the activity of XO activity under oxidative stress. Conclusion: our current findings suggest that BCAAs supplementation may potentially serve as a therapeutic target for treatment of oxidative stress occurs with atherosclerosis, IR-diabetes, MetS and tumorigenesis.

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THE EFFECT OF RHEUMATOID FACTORS AND OF ANTIGLOBULINS ON IMMUNE HEMOLYSIS IN VIVO

Journal of Experimental Medicine ◽

10.1084/jem.117.1.105 ◽

1963 ◽

Vol 117 (1) ◽

pp. 105-125 ◽

Cited By ~ 15

Author(s):

Manuel E. Kaplan ◽

James H. Jandl

Keyword(s):

Protein Content ◽

Blood Stream ◽

Body Fluids ◽

Red Cells ◽

Rheumatoid Factors ◽

Low Protein ◽

Immune Hemolysis

Studies were undertaken in man and in the rat comparing the effects of rheumatoid factors and immune antiglobulins on red cells sensitized with incomplete antibodies. The interaction of immune antiglobulins with sensitized red cells produced (a) agglutination in vitro and (b) an accelerated sequestration of the sensitized cells in vivo. In contrast, rheumatoid macroglobulins, although capable of agglutinating Rh-sensitized red cells in vitro, did not modify their destruction in vivo. The failure of rheumatoid factors to function as antiglobulins in vivo appears to reflect their non-reactivity with sensitized cells in whole serum. It is suggested: (a) that the native (7S) gamma globulins of plasma competitively inhibit rheumatoid factors from reacting with fixed antibody in the blood stream; (b) that if these macroglobulins do indeed have pathogenetic activity, this may be limited to body fluids of low protein content.

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Role of BrnQ1 and BrnQ2 in Branched-Chain Amino Acid Transport and Virulence in Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.02542-14 ◽

2014 ◽

Vol 83 (3) ◽

pp. 1019-1029 ◽

Cited By ~ 21

Author(s):

Julienne C. Kaiser ◽

Sameha Omer ◽

Jessica R. Sheldon ◽

Ian Welch ◽

David E. Heinrichs

Keyword(s):

Staphylococcus Aureus ◽

Virulence Gene ◽

Defined Medium ◽

Infection Model ◽

Content Type ◽

Virulence Gene Expression ◽

Branched Chain Amino Acid ◽

Branched Chain

The branched-chain amino acids (BCAAs; Ile, Leu, and Val) not only are important nutrients for the growth ofStaphylococcus aureusbut also are corepressors for CodY, which regulates virulence gene expression, implicating BCAAs as an important link between the metabolic state of the cell and virulence. BCAAs are either synthesized intracellularly or acquired from the environment.S. aureusencodes three putative BCAA transporters, designated BrnQ1, BrnQ2, and BrnQ3; their functions have not yet been formally tested. In this study, we mutated all threebrnQparalogs so as to characterize their substrate specificities and their roles in growthin vitroandin vivo. We demonstrated that in the community-associated, methicillin-resistantS. aureus(CA-MRSA) strain USA300, BrnQ1 is involved in uptake of all three BCAAs, BrnQ2 transports Ile, and BrnQ3 does not have a significant role in BCAA transport under the conditions tested. Of the three, only BrnQ1 is essential for USA300 to grow in a chemically defined medium that is limited for Leu or Val. Interestingly, we observed that abrnQ2mutant grew better than USA300 in media limited for Leu and Val, owing to the fact that this mutation leads to overexpression ofbrnQ1. In a murine infection model, thebrnQ1mutant was attenuated, but in contrast,brnQ2mutants had significantly increased virulence compared to that of USA300, a phenotype we suggest is at least partially linked to enhancedin vivoscavenging of Leu and Val through BrnQ1. These data uncover a hitherto-undiscovered connection between nutrient acquisition and virulence in CA-MRSA.

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High CD169 Monocyte/Lymphocyte Ratio Reflects the Immunophenotyping Disruption and Predicts Oxygen Need in COVID-19 Patients

10.20944/preprints202105.0731.v1 ◽

2021 ◽

Author(s):

Antonella Minutolo ◽

Vita Petrone ◽

Marialaura Fanelli ◽

Marco Iannetta ◽

Martina Giudice ◽

...

Keyword(s):

Disease Progression ◽

Inflammatory Markers ◽

Predictive Marker ◽

Pulmonary Involvement ◽

Mrna Levels ◽

Healthy Donors ◽

Respiratory Outcome ◽

Early Biomarker

Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.

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Profiles of Odd- and Branched-Chain Fatty Acids and Their Correlations With Rumen Fermentation Parameters, Microbial Protein Synthesis and Bacterial Populations Based on Pure Carbohydrate Incubation in Vitro

10.21203/rs.3.rs-68439/v1 ◽

2020 ◽

Author(s):

Hangshu Xin ◽

Xin Liu ◽

Xin Jiang ◽

Chunlong Liu ◽

Shuzhi Zhang ◽

...

Keyword(s):

Fatty Acids ◽

Volatile Fatty Acids ◽

Cellulolytic Bacteria ◽

Bacterial Populations ◽

Branched Chain Fatty Acids ◽

Degrading Bacteria ◽

Branched Chain ◽

Fermentation Parameters ◽

Chain Fatty Acids

Abstract Background: The objectives of this study were to evaluate the profiles of odd- and branched-chain fatty acids (OBCFA; including C15:0, iso-C15:0, anteiso-C15:0, iso-C16:0, C17:0, iso-C17:0 and anteiso-C17:0) during pure carbohydrates incubation in vitro and whether they correlated with ruminal fermentation parameters, microbial crude protein (MCP) synthesis, and bacterial populations. The pure substrates containing five different ratios of fiber and starch (F:S; 0:100, 25:75, 50:50, 75:25 and 100:0) were incubated for 6 h, 12 h, 18 h and 24 h. Results: Except iso-C17:0, OBCFA concentrations were interacted by F:S and incubation time. The highest concentration of total OBCFA was found in the fermented mixture after 24 h of incubation when the F:S = 0:100; while the lowest level was 1.65 mg/g DM produced after 6 h of incubation with F:S = 50:50. The concentrations of total volatile fatty acids (TVFA) and MCP remarkably decreased linearly as the inclusion of fiber in the substrates increased, as expected. The proportions of investigated cellulolytic bacteria in our study were increased linearly (or linearly and quadratically) while those of R. amylophilus and S. bovis were decreased as fiber inclusion increased. The correlation analysis indicated that iso-C16:0 concentration might have potential as a marker of productions of TVFA and MCP with ρ being 0.78 and 0.82 respectively. Compared to starch degrading bacteria, cellulolytic bacteria had more correlations with OBCFA profiles, and the strongest association was found on the population of R. flavefaciens with C15:0 concentration (ρ = 0.70). Conclusions: Our study shows there might be scope for iso-C16:0 to predict rumen productions of VFA and MCP. Notedly, this is the first paper reporting linkage of OBCFA with rumen function based on pure carbohydrate in vitro incubation, which would avoid confounding interference from dietary protein and fat presence. However, more in-depth experiments are needed to substantiate the current findings.

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Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104650118 ◽

2021 ◽

Vol 118 (23) ◽

pp. e2104650118

Author(s):

Jessica Cannavino ◽

Mengle Shao ◽

Yu A. An ◽

Svetlana Bezprozvannaya ◽

Shiuhwei Chen ◽

...

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Uncoupling Protein ◽

Rna Binding Protein ◽

Cold Environments ◽

Transport Chain ◽

Brown Adipose ◽

Mitochondrial Oxidation ◽

Branched Chain

Homeothermic vertebrates produce heat in cold environments through thermogenesis, in which brown adipose tissue (BAT) increases mitochondrial oxidation along with uncoupling of the electron transport chain and activation of uncoupling protein 1 (UCP1). Although the transcription factors regulating the expression of UCP1 and nutrient oxidation genes have been extensively studied, only a few other proteins essential for BAT function have been identified. We describe the discovery of FAM195A, a BAT-enriched RNA binding protein, which is required for cold-dependent thermogenesis in mice. FAM195A knockout (KO) mice display whitening of BAT and an inability to thermoregulate. In BAT of FAM195A KO mice, enzymes involved in branched-chain amino acid (BCAA) metabolism are down-regulated, impairing their response to cold. Knockdown of FAM195A in brown adipocytes in vitro also impairs expression of leucine oxidation enzymes, revealing FAM195A to be a regulator of BCAA metabolism and a potential target for metabolic disorders.

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Pharmacological modulation of cell functional activity with valproic acid and erythropoietin

Research Results in Pharmacology ◽

10.3897/rrpharmacology.5.34710 ◽

2019 ◽

Vol 5 (2) ◽

pp. 89-99

Author(s):

Polina A. Golubinskaya ◽

Marina V. Sarycheva ◽

Svetlana Y. Burda ◽

Maksim V. Puzanov ◽

Natalya A. Nadezhdina ◽

...

Keyword(s):

Valproic Acid ◽

Antiepileptic Drug ◽

Axial Skeleton ◽

Pharmacological Modulation ◽

Inhibition Of Growth ◽

Acid Effect ◽

Branched Chain ◽

Growth Of Tumor

Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.

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Effects of clofibric acid on the activity and activity state of the hepatic branched-chain 2-oxo acid dehydrogenase complex

Biochemical Journal ◽

10.1042/bj2850167 ◽

1992 ◽

Vol 285 (1) ◽

pp. 167-172 ◽

Cited By ~ 11

Author(s):

Y Zhao ◽

J Jaskiewicz ◽

R A Harris

Keyword(s):

Active Form ◽

Clofibric Acid ◽

Chow Diet ◽

Acid Dehydrogenase ◽

Low Protein ◽

Activity State ◽

Branched Chain ◽

Acid Dehydrogenase Complex ◽

Dehydrogenase Complex

Feeding clofibric acid to rats caused little or no change in total activity of the liver branched-chain 2-oxo acid dehydrogenase complex (BCODC). No change in mass of liver BCODC was detected by immunoblot analysis in response to dietary clofibric acid. No changes in abundance of mRNAs for the BCODC E1 alpha, E1 beta and E2 subunits were detected by Northern-blot analysis. Likewise, dietary clofibric acid had no effect on the activity state of liver BCODC (percentage of enzyme in the dephosphorylated, active, form) of rats fed on a chow diet. However, dietary clofibric acid greatly increased the activity state of liver BCODC of rats fed on a diet deficient in protein. No stable change in liver BCODC kinase activity was found in response to clofibric acid in either chow-fed or low-protein-fed rats. Clofibric acid had a biphasic effect on flux through BCODC in hepatocytes prepared from low-protein-fed rats. Stimulation of BCODC flux at low concentrations was due to clofibric acid inhibition of BCODC kinase, which in turn allowed activation of BCODC by BCODC phosphatase. Inhibition of BCODC flux at high concentrations was due to direct inhibition of BCODC by clofibric acid. The results suggest that the effects of clofibric acid in vivo on branched-chain amino acid metabolism can be explained by the inhibitory effects of this drug on BCODC kinase.

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