Dietary methionine level alters growth, digestibility, and gene expression of amino acid transporters in meat-type chickens

Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

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Increases in circulating amino acids with in-feed antibiotics correlated with gene expression of intestinal amino acid transporters in piglets

Amino Acids ◽

10.1007/s00726-017-2451-0 ◽

2017 ◽

Vol 49 (9) ◽

pp. 1587-1599 ◽

Cited By ~ 21

Author(s):

Miao Yu ◽

Chunlong Mu ◽

Yuxiang Yang ◽

Chuanjian Zhang ◽

Yong Su ◽

...

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Amino Acid Transporters

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Amino acid transporters: roles in amino acid sensing and signalling in animal cells

Biochemical Journal ◽

10.1042/bj20030405 ◽

2003 ◽

Vol 373 (1) ◽

pp. 1-18 ◽

Cited By ~ 231

Author(s):

Russell HYDE ◽

Peter M. TAYLOR ◽

Harinder S. HUNDAL

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Nutrient Availability ◽

Cellular Response ◽

Amino Acid Transporters ◽

Animal Cells ◽

Amino Acid Availability ◽

Altered Gene ◽

Amino Acid Sensing

Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid “receptors” function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms.

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Abstract 1185: Regulation of neutral amino acid transporters gene expression profile in non-small cell lung cancer

10.1158/1538-7445.am2015-1185 ◽

2015 ◽

Author(s):

Pierre P. Massion ◽

Maria Senosain ◽

Mohamed Hassanein ◽

Xiangming Ji ◽

Jun Qian ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Amino Acid ◽

Small Cell Lung Cancer ◽

Gene Expression Profile ◽

Expression Profile ◽

Cell Lung Cancer ◽

Small Cell ◽

Amino Acid Transporters ◽

Small Cell Lung

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Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+AT (Slc7a9) in mice

AJP Renal Physiology ◽

10.1152/ajprenal.00221.2013 ◽

2013 ◽

Vol 305 (12) ◽

pp. F1645-F1655 ◽

Cited By ~ 8

Author(s):

Andrea Di Giacopo ◽

Isabel Rubio-Aliaga ◽

Alessandra Cantone ◽

Ferruh Artunc ◽

Rexhep Rexhepaj ◽

...

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Membrane Vesicle ◽

Fractional Excretion ◽

Amino Acid Transporters ◽

Type I ◽

Loss Of Function ◽

Dibasic Amino Acid ◽

Knockout Animals

Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b 0,+ AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b0,+. No remarkable gene expression changes were observed in other amino acid transporters and the peptide transporters in the intestine and kidney. Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout animals compared with wild-type animals. The fractional excretion of arginine was increased as expected (∼100%), but fractional excretions of lysine (∼35%), ornithine (∼16%), and cystine (∼11%) were less affected. Loss of function of b0,+AT reduced transport of cystine and arginine in renal BBMVs and completely abolished the exchanger activity of dibasic amino acids with neutral amino acids. In conclusion, loss of Slc7a9 function decreases the GFR and increases the excretion of several amino acids to a lesser extent than expected with no clear regulation at the mRNA and protein level of alternative transporters and no increased renal epithelial uptake. These observations indicate that transporters located in distal segments of the kidney and/or metabolic pathways may partially compensate for Slc7a9 loss of function.

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Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders

Neuropsychobiology ◽

10.1159/000510886 ◽

2020 ◽

pp. 1-11

Author(s):

Julia Rode ◽

Lin Yang ◽

Julia König ◽

Ashley Nicole Hutchinson ◽

Rebecca Wall ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Amino Acid ◽

Affective Disorders ◽

Expression Profiles ◽

Human Fibroblasts ◽

Antioxidant Properties ◽

Amino Acid Transporters ◽

Potential Implication ◽

Cellular Models

Introduction: Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions. Objective: Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives. Methods: Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (3H) was used as a tracer to measure the transport of tryptophan across the cell membranes (n = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (n = 2). Results: As hypothesized,oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan. Conclusions:Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.

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Faculty Opinions recommendation of Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718116186.793484231 ◽

2014 ◽

Author(s):

Lars Malmstroem

Keyword(s):

Gene Expression ◽

Amino Acid ◽

Regulatory Protein ◽

Single Amino Acid ◽

Naturally Occurring

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Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽

10.3390/cancers13010125 ◽

2021 ◽

Vol 13 (1) ◽

pp. 125

Author(s):

Uğur Kahya ◽

Ayşe Sedef Köseer ◽

Anna Dubrovska

Keyword(s):

Amino Acid ◽

Cancer Metabolism ◽

Tumor Imaging ◽

Redox Homeostasis ◽

Amino Acid Uptake ◽

Metabolic Reprogramming ◽

Tumor Evolution ◽

Amino Acid Transporters ◽

Acid Uptake ◽

Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

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Pichia pastoris and the Recombinant Human Heterodimeric Amino Acid Transporter 4F2hc-LAT1: From Clone Selection to Pure Protein

Methods and Protocols ◽

10.3390/mps4030051 ◽

2021 ◽

Vol 4 (3) ◽

pp. 51

Author(s):

Satish Kantipudi ◽

Daniel Harder ◽

Sara Bonetti ◽

Dimitrios Fotiadis ◽

Jean-Marc Jeckelmann

Keyword(s):

Amino Acid ◽

Pichia Pastoris ◽

Protein Complexes ◽

Amino Acid Transporter ◽

Amino Acid Transporters ◽

Expression Host ◽

Amino Acids And Derivatives ◽

Heterodimeric Complex ◽

Acid Transporter ◽

And Function

Heterodimeric amino acid transporters (HATs) are protein complexes composed of two subunits, a heavy and a light subunit belonging to the solute carrier (SLC) families SLC3 and SLC7. HATs transport amino acids and derivatives thereof across the plasma membrane. The human HAT 4F2hc-LAT1 is composed of the type-II membrane N-glycoprotein 4F2hc (SLC3A2) and the L-type amino acid transporter LAT1 (SLC7A5). 4F2hc-LAT1 is medically relevant, and its dysfunction and overexpression are associated with autism and tumor progression. Here, we provide a general applicable protocol on how to screen for the best membrane transport protein-expressing clone in terms of protein amount and function using Pichia pastoris as expression host. Furthermore, we describe an overexpression and purification procedure for the production of the HAT 4F2hc-LAT1. The isolated heterodimeric complex is pure, correctly assembled, stable, binds the substrate L-leucine, and is thus properly folded. Therefore, this Pichia pastoris-derived recombinant human 4F2hc-LAT1 sample can be used for downstream biochemical and biophysical characterizations.

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