scholarly journals Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1

2021 ◽  
Vol 8 (7) ◽  
pp. 88
Author(s):  
Tianjiao Huang ◽  
John A. Terrell ◽  
Jay H. Chung ◽  
Chengpeng Chen
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Liver Cells ◽  
Urea Synthesis ◽  
Integrin Β1 ◽  
Flat Substrate ◽  
Intracellular Amino Acid ◽  
Vital Functions ◽  
Cytochrome P450 Activity ◽  
Amino Acid Levels

Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin β1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin β1 than cells on the microfibers. Moreover, after partially blocking integrin β1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin β1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).

scholarly journals The E3 ubiquitin ligase ZNRF2 is a substrate of mTORC1 and regulates its activation by amino acids

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Gerta Hoxhaj ◽  
Edward Caddye ◽  
Ayaz Najafov ◽  
Vanessa P Houde ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Protein Phosphatase ◽  
E3 Ubiquitin Ligase ◽  
Mechanistic Target Of Rapamycin ◽  
Rag Gtpases ◽  
Intracellular Amino Acid ◽  
Amino Acid Levels ◽  
Amino Acid Sensing

The mechanistic Target of Rapamycin complex 1 (mTORC1) senses intracellular amino acid levels through an intricate machinery, which includes the Rag GTPases, Ragulator and vacuolar ATPase (V-ATPase). The membrane-associated E3 ubiquitin ligase ZNRF2 is released into the cytosol upon its phosphorylation by Akt. In this study, we show that ZNRF2 interacts with mTOR on membranes, promoting the amino acid-stimulated translocation of mTORC1 to lysosomes and its activation in human cells. ZNRF2 also interacts with the V-ATPase and preserves lysosomal acidity. Moreover, knockdown of ZNRF2 decreases cell size and cell proliferation. Upon growth factor and amino acid stimulation, mTORC1 phosphorylates ZNRF2 on Ser145, and this phosphosite is dephosphorylated by protein phosphatase 6. Ser145 phosphorylation stimulates vesicle-to-cytosol translocation of ZNRF2 and forms a novel negative feedback on mTORC1. Our findings uncover ZNRF2 as a component of the amino acid sensing machinery that acts upstream of Rag-GTPases and the V-ATPase to activate mTORC1.

Interrelationship between hepatic ureagenesis and gluconeogenesis in early sepsis

1991 ◽  
Vol 260 (3) ◽  
pp. E453-E458 ◽  
Author(s):  
Y. Ohtake ◽  
M. G. Clemens
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Substrate Preference ◽  
Hormone Sensitivity ◽  
Urea Production ◽  
Urea Release ◽  
Amino Acid Levels ◽  
Early Sepsis ◽  
Septic Group

This study was performed to investigate the interrelationship between gluconeogenesis and ureagenesis during sepsis. In isolated perfused livers, gluconeogenesis was assessed using either lactate or a combination of lactate, glutamine, and alanine as substrate. Ureagenesis was assessed using either NH4Cl or glutamine plus alanine as substrate. NH4Cl stimulated urea production in livers from both septic and sham-operated control rats. Urea release was approximately 1.2 and 2.0 mg urea nitrogen.g-1.h-1 for 1 and 5 mM NH4Cl, respectively, and was equal for both groups. With amino acids as substrate, urea production was significantly greater in livers from septic animals compared with controls. Phenylephrine stimulated urea production in the sham-operated group by about twofold, whereas in the septic group urea release was slightly inhibited. Gluconeogenesis from lactate was inhibited by NH4Cl (1 and 5 mM) in both groups, with no difference between groups. In contrast to enhanced ureagenesis from amino acids in septic rats, gluconeogenesis was decreased by approximately 24% (P less than 0.5). Similarly, phenylephrine (1 microM) stimulated gluconeogenesis by 13 +/- 1 mumol.g-1.h-1 in sham-operated rats but only by 9 +/- 1 mumol.g-1.h-1 in septic rats (P less than 0.02). These results suggest that hepatic gluconeogenic and ureagenic pathways are intact in sepsis but that altered substrate preference and hormone sensitivity may result in decreased gluconeogenesis in the presence of elevated amino acid levels.

scholarly journals Amino acids whose intracellular levels change most during aging alter chronological lifespan of fission yeast

2020 ◽  
Author(s):  
Charalampos Rallis ◽  
Michael Mülleder ◽  
Graeme Smith ◽  
Yan Zi Au ◽  
Markus Ralser ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Fission Yeast ◽  
Yeast Cells ◽  
Total Amino Acid ◽  
Wild Type ◽  
Chronological Lifespan ◽  
Biomarkers Of Aging ◽  
Concentration Changes ◽  
Amino Acid Levels

AbstractAmino acid deprivation or supplementation can affect cellular and organismal lifespan, but we know little about the role of concentration changes in free, intracellular amino acids during aging. Here, we determine free amino-acid levels during chronological aging of non-dividing fission yeast cells. We compare wild-type with long-lived mutant cells that lack the Pka1 protein of the protein kinase A signalling pathway. In wild-type cells, total amino-acid levels decrease during aging, but much less so in pka1 mutants. Two amino acids strongly change as a function of age: glutamine decreases, especially in wild-type cells, while aspartate increases, especially in pka1 mutants. Supplementation of glutamine is sufficient to extend the chronological lifespan of wild-type but not of pka1Δ cells. Supplementation of aspartate, on the other hand, shortens the lifespan of pka1Δ but not of wild-type cells. Our results raise the possibility that certain amino acids are biomarkers of aging, and their concentrations during aging can promote or limit cellular lifespan.

Effect of free fatty acids on blood amino acid levels in human

1986 ◽  
Vol 250 (6) ◽  
pp. E686-E694 ◽  
Author(s):  
E. Ferrannini ◽  
E. J. Barrett ◽  
S. Bevilacqua ◽  
R. Jacob ◽  
M. Walesky ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Insulin ◽  
Plasma Free Fatty Acid ◽  
Blood Levels ◽  
Experimental Conditions ◽  
Lipid Infusion ◽  
Amino Acid Levels ◽  
Branched Chain

Raised plasma free fatty acid (FFA) levels effectively impede glucose uptake in vivo, thereby conserving plasma glucose and sparing glycogen. To test whether FFA have any effect on blood amino acid levels, we infused Intralipid plus heparin or saline into healthy volunteers under four different experimental conditions: A) overnight fast; B) euglycemic hyperinsulinemia (approximately 100 microU/ml); C) hyperglycemic (approximately 200 mg/100 ml) hyperinsulinemia (approximately 50 microU/ml); and D) hyperglycemic (approximately 300 mg/100 ml) normoinsulinemia (approximately 20 microU/ml). In the fasting state (A), lipid infusion was associated with lower blood levels of most amino acids, both branched chain and glucogenic. This effect, however, could not be ascribed to lipid infusion alone, because plasma insulin levels were also stimulated. The clamp studies (B, C, and D) allowed to assess the influence of lipid on blood amino acid levels at similar plasma insulin and glucose levels. It was thus observed that lipid infusion has a significant hypoaminoacidemic effect of its own under both euglycemic (B) and hyperglycemic (C) conditions; this effect involved many glucogenic amino acids (alanine, glycine, phenylalanine, serine, threonine, and cystine) but none of the branched-chain amino acids (leucine, isoleucine, and valine). In marked contrast, normoinsulinemic hyperglycemia (D), with or without lipid infusion, caused no change in the blood level of any measured amino acid. We conclude that lipid infusion has a hypoaminoacidemic action. We also suggest that this action is permitted by insulin and may involve specific metabolic interactions (e.g., reduced availability of glucose-derived pyruvate or glycerophosphate) as well as enhanced uptake by the liver.

Acute acidosis inhibits liver amino acid transport: no primary role for the urea cycle in acid-base balance

1994 ◽  
Vol 267 (6) ◽  
pp. F1015-F1020 ◽  
Author(s):  
L. Boon ◽  
P. J. Blommaart ◽  
A. J. Meijer ◽  
W. H. Lamers ◽  
A. C. Schoolwerth
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hepatic Vein ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Primary Role ◽  
Urea Synthesis ◽  
Acid Transport ◽  
Acid Base

To examine further the role of the liver in acid-base homeostasis, we studied hepatic amino acid uptake and urea synthesis in rats in vivo during acute acidosis and alkalosis, induced by infusion of 1.8 mmol of HCl or NaHCO3 over 3 h. Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic plasma, and arteriovenous differences of amino acids and urinary urea and NH4+ excretion were measured. In acidosis, urinary urea excretion was reduced 36% (P < 0.01), whereas urinary NH4+ excretion increased ninefold (P < 0.01), but the sum of urea and NH4+ excretion was unchanged. Total hepatic amino acid uptake, as determined from arteriovenous differences, was decreased by 63% (P < 0.01) in acidosis, with the major effect being noted with alanine and glycine. Only glutamine was released in both acidosis and alkalosis but was not significantly different in the two conditions. Since intracellular concentrations of readily transportable amino acids were not different at low pH despite accelerated protein degradation, these results indicate that hepatic amino acid transport was inhibited markedly and sufficiently to explain the observed decrease in urea synthesis. Total hepatic vein amino acid content was greater in acidosis than alkalosis (P < 0.01). Directly or indirectly, by conversion to glutamine elsewhere, these increased amino acids were degraded in kidney and accounted for the ninefold increase in urinary NH4+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular osmoregulatory role of amino acids and urea in marine elasmobranchs

1976 ◽  
Vol 230 (4) ◽  
pp. 925-931 ◽  
Author(s):  
RP Forster ◽  
L Goldstein
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Extracellular Fluid ◽  
Raja Erinacea ◽  
Urea Content ◽  
Intracellular Amino Acid ◽  
Trimethylamine Oxide ◽  
Total Amino Acids ◽  
Positive Materials

Little skates, Raja erinacea, and stingrays, Dasyatis americana, were gradually transferred over a period of 4-5 days from full strength to approximatley 50% seawater. Plasma and muscle osmolarity fell. Hematocrits were essentially unchanged. Extracellular fluid volume (ECF) of muscle, estimated as the chloride space, increased 70% during this period. Regulation of muscle cell volume was associated with sharp declines in cellular concentrations of total amino acids (ninhydrin-positive materials) and urea. The osmoregulatory importance of the free amino acid pool in erythrocytes and muscle was a particularly prominent feature in both species. Intracellular amino acid concentration in R. erinacea muscle fell from 214 to 144 mmol/liter during transfer to 50% seawater, urea from 398 to 264, and trimethylamine oxide (TMAO) dropped from 63.9 to 35.8 mmol/liter. TMAO plasma levels were similar in stingray and skate, but muscle TMAO concentrations were much higher in the former. Urea content in stingray plasma greatly exceeded that in R. erinacea-630 and 574 mmol/liter in two specimens-perhaps the highest recorded.

scholarly journals Diet, Physical Activity and Adiposity as Determinants of Circulating Amino Acid Levels in a Multiethnic Asian Population

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2603 ◽  
Author(s):  
Samuel H. Gunther ◽  
Chin Meng Khoo ◽  
Xueling Sim ◽  
E Shyong Tai ◽  
Rob M. van Dam
Keyword(s):  
Physical Activity ◽  
Amino Acids ◽  
Amino Acid ◽  
Multiple Testing ◽  
Asian Population ◽  
Lifestyle Factors ◽  
Health Examination ◽  
Activity Data ◽  
Study Program ◽  
Amino Acid Levels

Profiles of circulating amino acids have been associated with cardiometabolic diseases. We investigated the associations between dietary protein intake, physical activity and adiposity and serum amino acid profiles in an Asian population. We used data from 3009 male and female participants from the Singapore Prospective Study Program cohort. Dietary and physical activity data were obtained from validated questionnaires; anthropometric measurements were collected during a health examination; and fasting concentrations of 16 amino acids were measured using targeted LC-MS. The association between lifestyle factors and amino acid levels was modeled using multiple linear regression with adjustment for other sociodemographic and lifestyle factors and correction for multiple testing. We observed significant associations between seafood intake (β-coefficient 0.132, 95% CI 0.006, 0.257 for a 100% increment), physical activity (β-coefficient −0.096, 95% CI −0.183, −0.008 in the highest versus lowest quartile) and adiposity (BMI β-coefficient 0.062, 95% CI 0.054, 0.070 per kg/m2; waist circumference β-coefficient 0.034, 95% CI 0.031, 0.037 per cm) and branched-chain amino acid levels (expressed per-SD). We also observed significant interactions with sex for the association between meat and seafood and total intakes and BCAA levels (P for interaction 0.007), which were stronger in females than in males. Our findings suggest novel associations between modifiable lifestyle factors and amino acid levels in Asian populations.

Amino Acid Absorption following Intraperitoneal Administration in CAPD Patients

1981 ◽  
Vol 2 (3) ◽  
pp. 124-130 ◽  
Author(s):  
Paul F. Williams ◽  
Errol B. Marliss ◽  
G. Harvey Anderson ◽  
Arie Oren ◽  
Arthur N. Stein ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Acid Solution ◽  
Intraperitoneal Administration ◽  
Amino Acid Solution ◽  
Dialysis Solution ◽  
Term Administration ◽  
Osmotic Agent ◽  
Amino Acid Levels

Six non-diabetic CAPD patients were infused over six hours with two litres of a dialysis solution containing 2 g/ dl amino acids (a mixture of essentials and non-essentials). The osmolality of the solution and the amount of ultrafiltration it induced were simiiar to that of a 4.25 g% dextrose Dianeal solution (control), suggesting that an amino acid solution is an efficient osmotic agent. By the end of the six-hour infusion, 80 to 90% of the amino acids present in the dialysis solution had been absorbed. One hour after the infusion was instituted, plasma amino acid levels increased threefold and subsequently decreased to near the initial value by the sixth hour. The amino acid solution was as effective as the dextrose solution in removing urea nitrogen, creatinine and potassium. Our data indicate that intraperitoneal administration of amino acids is effective and well-tolerated in patients on CAPD. We believe further work should be done to determine whether long-term administration of amino acids by this route will improve the nutritional status of these patients and prevent the side effects of daily absorption of large amounts of glucose.

Variations in the concentrations of free amino acids in the plasma of the dairy cow at parturition

1972 ◽  
Vol 39 (3) ◽  
pp. 355-364 ◽  
Author(s):  
R. Verbeke ◽  
E. Roets ◽  
G. Peeters
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino ◽  
Milk Protein ◽  
Sampling Period ◽  
Aminobutyric Acid ◽  
Amino Acid Utilization ◽  
Amino Acid Levels ◽  
The Mean ◽  
Peak Value

SummaryThe plasma levels of individual amino acids were studied in 6 dairy cows from 4 days before to 3 days after calving. During this sampling period, the concentrations of 13 amino acids showed significant changes. The levels of several amino acids were depressed markedly in the sample collected immediately before calving. Following parturition, the concentration of most amino acids gradually returned to values obtained 3 days before calving. The glutamine and alanine contents of the plasma rose to a peak value 1 day after calving and subsequently decreased. The mean concentrations of glycine and α-aminobutyric acid did not change before parturition but rose significantly thereafter. These observations are discussed in terms of amino-acid utilization for milk protein synthesis and gluconeogenesis at the onset of lactation. The changes in plasma amino acid levels appear to be synchronized with those reported for prolactin and progesterone in the 24 h before parturition. This may indicate an important influence of both hormones on the lactogenic process in the cow. The highly significant correlations obtained between the concentrations of 14 individual amino acids are discussed.

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