scholarly journals Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue ofPept2−/−mice

2007 ◽  
Vol 28 (3) ◽  
pp. 301-310 ◽  
Author(s):  
Isabelle M. Frey ◽  
Isabel Rubio-Aliaga ◽  
Anne Siewert ◽  
Daniela Sailer ◽  
Aleksey Drobyshev ◽  
...  

PEPT2 is an integral membrane protein in the apical membrane of renal epithelial cells that operates as a rheogenic transporter for di- and tripeptides and structurally related drugs. Its prime role is thought to be the reabsorption of filtered di- and tripeptides contributing to amino acid homeostasis. To elucidate the role of PEPT2 in renal amino acid metabolism we submitted kidney tissues of wild-type and a Pept2−/−mouse line to a comprehensive transcriptome, proteome and metabolome profiling and analyzed urinary amino acids and dipeptides. cDNA microarray analysis identified 147 differentially expressed transcripts in transporter-deficient animals, and proteome analysis by 2D-PAGE and MALDI-TOF-MS identified 37 differentially expressed proteins. Metabolite profiling by GC-MS revealed predominantly altered concentrations of amino acids and derivatives. Urinary excretion of amino acids demonstrated increased glycine and cysteine/cystine concentrations and dipeptides in urine were assessed by amino acid analysis of urine samples before and after in vitro dipeptidase digestion. Dipeptides constituted a noticeable fraction of urinary amino acids in Pept2−/−animals, only, and dipeptide-bound glycine and cystine were selectively increased in Pept2−/−urine samples. These findings were confirmed by a drastically increased excretion of cysteinyl-glycine (cys-gly). Urinary loss of cys-gly together with lower concentrations of cysteine, glycine, and oxoproline in kidney tissue and altered expression of mRNA and proteins involved in glutathione (GSH) metabolism suggests that PEPT2 is predominantly a system for reabsorption of cys-gly originating from GSH break-down, thus contributing to resynthesis of GSH.

1980 ◽  
Vol 26 (13) ◽  
pp. 1804-1808 ◽  
Author(s):  
M Y Tsai ◽  
J G Marshall ◽  
M W Josephson

Abstract We measured 11 amino acids in untimed urine samples, to determine whether such samples are suited for use in diagnosis of aminoacidurias. Results for untimed samples varied by as much as 25% more than for 24-h collections when amino acid excretions were expressed in terms of urinary creatinine. Values decreased with increasing age for either type of specimen. Urinary amino acid excretions were also determined with untimed or 24-h samples from patients with cystinuria. Lowe’s syndrome, nonketotic hyperglycinemia, or phenylketonuria. In all cases studied, the amino acids diagnostic of the diseases significantly exceeded the reference interval obtained for 260 control subjects in six age categories. We conclude that untimed urine samples can be used for diagnosis of these inborn errors of amino acid metabolism, but further studies are needed to evaluate their usefulness for other metabolic disorders.


1969 ◽  
Vol 15 (7) ◽  
pp. 545-554 ◽  
Author(s):  
Milton L Maskaleris ◽  
Stanislaw Gross ◽  
Ade T Milhorat

Abstract An amino acid AutoAnalyzer was used to monitor the excretion patterns of the urinary amino acids and peptides of 7 male patients (aged 3-17) with muscular dystrophy of the Duchenne type. In comparison with the output of 8 healthy boys (aged 3-12), on the average, a reduction in the excretion of Thr, Ser, Gly, Ala, Val, Ile, Tyr, Lys, and His over a 24-hr period was found in the urine of the patients, although the number of analyses was too small for statistically significant conclusions. The content of Asp, Glu, Phe, and Leu was about equal, and Pro and Hyp were present in very small quantities. Also, for the first time, a peptide analyzer was used to study the bound components from urine specimens of the patients. Excretion patterns of several peptides in three of the above patients aged 3-17 were found to differ from those of the controls. Of the six major peptide fractions examined, five were present in smaller amounts in the urine of patients; only one was elevated. It appears from these preliminary results that further study of the excretion patterns of amino acids and peptides of dystrophic patients is worthwhile, and that study of the peptides should be given preference.


1969 ◽  
Vol 62 (3) ◽  
pp. 513-520 ◽  
Author(s):  
M Zachmann

ABSTRACT Amino acids in the plasma and urine of 6 hypopituitary dwarfs before and after 3–5 days of human growth hormone (HGH) administration (2 mg/m2 daily) were studied. As reported previously, the concentrations of several amino acids in the plasma of untreated hypopituitary dwarfs are low. After administration of HGH certain amino acids in the plasma increased regularly (threonine, serine, glycine, methionine and others) and the overall amino acid pattern in the plasma became normal. Other amino acids did not show consistent changes. The changes in the plasma concentrations do not seem to be related to renal mechanisms, since urinary amino acids and amino acid clearances varied only little. The HGH induced increase of plasma amino acids affects different amino acids than those involved in the increase of plasma amino acids induced by puberty in the male. This suggests that HGH and testosterone have different effects on the amino acid metabolism.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Martha L Daviglus ◽  
Jeremiah Stamler ◽  
Queenie Chan ◽  
Ian J Brown ◽  
Alan R Dyer ◽  
...  

Background: Available data indicate inverse relations to blood pressure (BP) of dietary vegetable protein and its main amino acid, glutamic acid, also direct relations to BP of meat and animal protein intakes. Data on association of urinary amino acids (UAAs) with BP are limited. Objective: To assess the relationship between UAAs and BP. Methods: This study assessed relations to BP of 21 urinary amino acids among 4,677 men and women ages 40-59 (17 population samples in China, Japan, UK, USA) from the International Study on Macro/Micronutrients and Blood Pressure (INTERMAP). Urinary amino acid excretion was expressed as log transformed value of each urinary amino acid (μmol/24 h), and as % dietary total protein (based on urinary urea nitrogen excretion). Results: In multivariate analyses with all 21 UAAs considered together, independent inverse relations to BP were found for serine, glycine, and lysine, and independent direct relations to BP for threonine, cystine, and 3-methylhistidine, controlling for possible non-dietary and dietary confounders (including body mass index and each of the other UAAs). For example, with log urinary serine at 75th compared to the 25th percentile, SBP/DBP was lower by 2.4/1.8 mm Hg and 2.2/1.7 mm Hg on average without and with adjustment for body mass index in multivariate models. With log urinary 3-methylhistidine at 75th compared to the 25th percentile, SBP/DBP was higher by 3.8/2.7 and 1.6/1.4 mm Hg. Conclusions: These significant new findings on relations to blood pressure of urinary amino acids need to be verified by additional - including prospective - data.


1975 ◽  
Vol 21 (13) ◽  
pp. 1970-1975 ◽  
Author(s):  
Henri Dirren ◽  
Arthur B Robinson ◽  
Linus Pauling

Abstract The urinary amino acid profiles of 79 young women and 72 young men were studied with an automated high-pressure amino acid analyzer. A nonparametric statistical analysis was applied for detecting profile differences related to sex and other variables. A strong sex-related pattern was confirmed and its power for sex determination was evaluated. For the women, profile differences related to the use of oral contraceptives were also discovered and evaluated. No correlation with the menstrual cycle was detected.


1955 ◽  
Vol 215 (1) ◽  
pp. 111-124 ◽  
Author(s):  
Henry Borsook ◽  
Adolph Abrams ◽  
Peter H. Lowy

2021 ◽  
Vol 22 (12) ◽  
pp. 6252
Author(s):  
Paula Ossowicz-Rupniewska ◽  
Rafał Rakoczy ◽  
Anna Nowak ◽  
Maciej Konopacki ◽  
Joanna Klebeko ◽  
...  

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.


2015 ◽  
Vol 24 (4) ◽  
pp. 197-205
Author(s):  
Dwi Wulandari ◽  
Lisnawati Rachmadi ◽  
Tjahjani M. Sudiro

Background: E6 and E7 are oncoproteins of HPV16. Natural amino acid variation in HPV16 E6 can alter its carcinogenic potential. The aim of this study was to analyze phylogenetically E6 and E7 genes and proteins of HPV16 from Indonesia and predict the effects of single amino acid substitution on protein function. This analysis could be used to reduce time, effort, and research cost as initial screening in selection of protein or isolates to be tested in vitro or in vivo.Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of  Indonesian isolates, which  were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP.Results: Java variants and isolate ui66* belonged to European branch, while the others belonged to Asian and African branches. Twelve changes of amino acids were found in E6 and one in E7 proteins. SNAP analysis showed two non neutral mutations, i.e. R10I and C63G in E6 proteins. R10I mutations were found in Af-2 genotype (AF472509) and Indonesian isolates (Af2*), while C63G mutation was found only in Af2*.Conclusion: E6 proteins of HPV16 variants were more variable than E7. SNAP analysis showed that only E6 protein of African-2 branch had functional differences compared to HPV16R.


1971 ◽  
Vol 121 (5) ◽  
pp. 817-827 ◽  
Author(s):  
R. C. Hider ◽  
E. B. Fern ◽  
D. R. London

1. The kinetics of radioactive labelling of extra- and intra-cellular amino acid pools and protein of the extensor digitorum longus muscle were studied after incubations with radioactive amino acids in vitro. 2. The results indicated that an extracellular pool could be defined, the contents of which were different from those of the incubation medium. 3. It was concluded that amino acids from the extracellular pool, as defined in this study, were incorporated directly into protein.


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