scholarly journals POS0421 COMBINED ANALYSIS OF METABOLIC AND TRANSCRIPTOMIC KIDNEY PROFILES OF NZW/B-F1 MURINE LUPUS UNCOVERS BIOLOGICAL MECHANISMS PRECEDING THE ONSET OF NEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 439.2-440
Author(s):  
T. Manolakou ◽  
I. Tsiara ◽  
D. Nikolopoulos ◽  
P. Garantziotis ◽  
D. Benaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Differentially Expressed Genes ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Univariate Analysis ◽  
Differentially Expressed ◽  
Disease Stage ◽  
Cellular Respiration ◽  
H Nmr

Background:Metabolic pathways are important regulators of immune differentiation and activation in kidneys. Kidneys directly impact systemic metabolism, circulating metabolite levels, and express intrinsic metabolic activity. The integration of renal metabolomic and transcriptomic profiles may unravel unique gene-metabolite pairs of biological significance in lupus nephritis (LN).Objectives:To decipher gene-metabolite signatures at both pre-nephritic and nephritic stages of lupus.Methods:Kidneys were isolated and snap-frozen after perfusion from female NZB/NZW-F1 lupus mice at the pre-nephritic (3-month-old) and nephritic (6-month-old exhibiting ≥100 ng/dL of urine protein) stage of lupus (n=6/group). Age-matched female C57BL/6 mice were used as healthy controls. Sample extracts were used for RNA sequencing and 1H-NMR spectroscopy metabolic profiling. DESeq2 was used to identify differentially expressed genes. Univariate analysis was used to reveal metabolic differences characteristic for nephritis.Results:Comparative transcriptomic analyses uncovered multiple transcripts related to metabolic pathways: In pre-nephritic kidneys, lipid metabolism, cellular respiration, TCA cycle, amino acid metabolism processes were overrepresented in the upregulated genes while in nephritic kidneys, amino acid metabolism processes were overrepresented among the downregulated genes (Figure 1). 1H-NMR analysis revealed a total of 49 metabolites. Comparison of the metabolic levels of nephritic and pre-nephritic animals revealed that ADP, ATP, NAD+, Taurine and Myo-inositol decreased, while Thr increased significantly. The comparison to corresponding control animals, demonstrated that only myo-inositol increased significantly. Integration of kidney metabolomics and transcriptomics indicated the involvement of processes related to glutathione metabolism, leukocyte trans-endothelial migration and antigen presentation during the established renal disease stage.Conclusion:The combined transcriptomics and metabolomics analysis revealed metabolic derangements in lupus-affected kidneys both during subclinical and overt LN. Deregulated tissue-levels of taurine and myo-inositol at the subclinical stage of the disease suggest aberrant renal biochemistry preceding the development of overt LN that may directly impact systemic metabolism and circulating metabolite levels.Figure 1.Pathways linked to cell metabolism were overrepresented among 3-month upregulated and 6-month lupus mice (F1) downregulated DEGS (differentially expressed genes) compared to controls (C57BL/6).Acknowledgements:This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390).Disclosure of Interests:None declared

scholarly journals 557. Impact of Heavy Metal Exposure in the Transcriptional Response of Methicillin--Resistant Staphylococcus aureus (MRSA)-USA300 Latin-American Variant (USA300-LV)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S264-S265
Author(s):  
Aura M Echeverri ◽  
Sandra Rincon ◽  
Sebastian Solano ◽  
Rafael Rios ◽  
Lina P Carvajal ◽  
...  
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Functional Groups ◽  
Differentially Expressed Genes ◽  
Unknown Function ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Differentially Expressed ◽  
Host Immune System ◽  
Qrt Pcr

Abstract Background USA 300-LV is the predominant MRSA clone in Colombia and contains a genomic island designated “COMER” with genes for copper (Cu) and mercury (Hg) resistance. HM environmental contamination is a serious threat to public health in Colombia and could also influence the selection and evolution of HM resistance genes in MRSA. Here, we investigate the global transcriptomic responses of USA300-LV after exposure to HM under the hypothesis that USA300-LV strains are highly capable of sustaining higher HM concentrations Methods We performed comparative RNAseq experiments in USA300-LV clinical strain (CA-MRSA12). Total RNA was isolated in exponential phase in the absence and presence of sub-inhibitory concentrations of Cu and Hg (3 replicates). cDNA libraries were prepared and sequenced on an Illumina platform. Differentially expressed genes (DEG) were calculated by DeSeq2 (p-adjusted value ˂ 0.01) and results on 19 selected genes were confirmed by qRT-PCR. Results US300-LV exhibited a larger number of differentially expressed genes when exposed to Hg (n = 114) compared with Cu treatment (n = 16). The most common functional groups of genes upregulated after Hg exposure included those involved in amino acid metabolism (n = 18). In contrast, 45 genes were downregulated after Hg exposure, mostly associated to host immune system defense (n = 11). qRT-PCR confirmed that the most upregulated genes were those involved in murein hydrolase activity, Hg resistance and the transcriptional regulator Cro/CI. Of 9 genes that were downregulated, functional groups included ype VII secretion system, immune modulators and leucocidins. Copper treatment resulted in only 12 genes that were upregulated including those in the COMER element (n = 6), aminoacid metabolism (n = 3), ROS response (n = 1), host immune system defense (n = 1) and unknown function (n = 1). Downregulated genes were those associated to host immune system defense (n = 2), energy generation (n = 1) and unknown function (n = 1). Conclusion Differential adaptive responses after exposure to HM in USA300-LV suggest a role in the evolution of antimicrobial resistance and successful spread in the region. Metabolic adaptations involving amino acid metabolism seem to play a role in the evolution of HM resistance in MRSA. Disclosures All authors: No reported disclosures.

scholarly journals Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang
Keyword(s):  
Salt Stress ◽  
Amino Acid ◽  
Salt Tolerance ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Enrichment Analysis ◽  
Extracellular Region ◽  
Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Metabolic Pathways ◽  
Essential Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Redox Status ◽  
Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

2021 ◽  
Author(s):  
Yanjuan Liu ◽  
Qi Zeng ◽  
Wen Xiao ◽  
Fang Chen ◽  
Lianhong Zou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Dynamic Change ◽  
Sepsis Group ◽  
Control Group ◽  
Multivariate Statistical ◽  
Xuebijing Injection ◽  
Kegg Pathway Analysis

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

BIOCHEMICAL STUDIES OF AN UNNATURAL AND ANTITUMOR AMINO ACID: 1-AMINOCYCLOPENTANECARBOXYLIC ACID: II. EFFECTS ON CELLULAR RESPIRATION AND AMINO ACID METABOLISM

1962 ◽  
Vol 40 (1) ◽  
pp. 433-436 ◽  
Author(s):  
L. Berlinguet ◽  
Nicole Bégin ◽  
L. M. Babineau ◽  
R. O. Laferté
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Radioactive Substance ◽  
Cellular Respiration ◽  
Rat Tissues ◽  
Metabolic Products ◽  
Biochemical Studies

1-Aminocyclopentanecarboxylic acid (ACPC) was studied for its effect on cellular respiration of rat tissues and for its reactivity towards decarboxylases, transaminases, and amino acid oxidases. In the tissues studied, cellular respiration was normal. The amino acid was not decarboxylated, transaminated, or oxidized. The transamination and oxidation of other amino acids remained normal even in the presence of ACPC.Using the radioactive substance, it was found that the molecule remains intact within the cells since no metabolic products could be detected.

scholarly journals Comparative Proteomics Reveals the Spoilage-Related Factors of Shewanella putrefaciens Under Refrigerated Condition

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengkai Yi ◽  
Jing Xie
Keyword(s):  
Amino Acid ◽  
Proteomic Analysis ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Shewanella Putrefaciens ◽  
Extracellular Proteins ◽  
Differentially Expressed ◽  
Differentially Expressed Protein ◽  
Fish Proteins

Shewanella putrefaciens is a microorganism with strong spoilage potential for aquatic products. This study aimed to investigate the potential spoilage factors of S. putrefaciens by comparative proteomic analysis. The spoilage potential of two strains of S. putrefaciens (00A and 00B) isolated from chilled spoiled bigeye tuna was investigated. The results of total volatile basic nitrogen (TVB-N), trimethylamine (TMA) in fish inoculated with S. putrefaciens, extracellular protease activity of S. putrefaciens, and degradation of fish proteins indicated that the spoilage potential of S. putrefaciens 00A was much higher than that of 00B. Fish proteins are usually degraded by spoilage microorganism proteases into small molecular peptides and amino acids, which are subsequently degraded into spoilage metabolites in bacterial cells, leading to deterioration of fish quality. Thus, proteomic analysis of the extracellular and intracellular proteins of 00A vs. 00B was performed. The results indicated that the intracellular differentially expressed protein (IDEP) contained 243 upregulated proteins and 308 downregulated proteins, while 78 upregulated proteins and 4 downregulated proteins were found in the extracellular differentially expressed protein (EDEP). GO annotation revealed that IDEP and EDEP were mainly involved in cellular and metabolic processes. KEGG annotation results showed that the upregulated proteins in IDEP were mainly involved in sulfur metabolism, amino acid metabolism, and aminoacyl-tRNA biosynthesis, while downregulated proteins were related to propanoate metabolism. In contrast, EDEP of KEGG annotation was mainly involved in ribosomes, quorum sensing, and carbohydrate metabolism. Proteins associated with spoilage containing sulfur metabolism (sulfite reductase, sulfate adenylyltransferase, adenylyl-sulfate kinase), amino acid metabolism (biosynthetic arginine decarboxylase, histidine ammonia-lyase), trimethylamine metabolism (trimethylamine-N-oxide reductase), and extracellular proteins (ATP-dependent Clp protease proteolytic subunit) were identified as upregulated. These proteins may play a key role in the spoilage potential of S. putrefaciens. These findings would contribute to the identification of key spoilage factors and understanding of the spoilage mechanism of microorganisms.

scholarly journals Comparative Proteomics Reveals Cold Acclimation Machinery Through Enhanced Carbohydrate and Amino Acid Metabolism in Wucai (Brassica Campestris L.)

Plants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 474
Author(s):  
Lingyun Yuan ◽  
Shilei Xie ◽  
Libing Nie ◽  
Yushan Zheng ◽  
Jie Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cold Acclimation ◽  
Low Temperatures ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
Differentially Expressed Proteins ◽  
Limited Information

Limited information is available on the cold acclimation of non-heading Chinese cabbage (NHCC) under low temperatures. In this study, the isobaric tags for relative and absolute quantification (iTRAQ) were used to illustrate the molecular machinery of cold acclimation. Compared to the control (Cont), altogether, 89 differentially expressed proteins (DEPs) were identified in wucai leaves responding to low temperatures (LT). Among these proteins, 35 proteins were up-regulated ((and 54 were down-regulated). These differentially expressed proteins were categorized as having roles in carbohydrate metabolism, photosynthesis and energy metabolism, oxidative defense, amino acid metabolism, metabolic progress, cold regulation, methylation progress, and signal transduction. The fructose, glucose, and sucrose were dramatically increased in response to cold acclimation. It was firstly reported that aspartate, serine, glutamate, proline, and threonine were significantly accumulated under low temperatures. Results of quantitative real-time PCR analysis of nine DEPs displayed that the transcriptional expression patterns of six genes were consistent with their protein expression abundance. Our results demonstrated that wucai acclimated to low temperatures through regulating the expression of several crucial proteins. Additionally, carbohydrate and amino acid conversion played indispensable and vital roles in improving cold assimilation in wucai.

scholarly journals Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation-Induced Metabolic Networks in Human T cells

2019 ◽  
Author(s):  
S. Hiemer ◽  
S. Jatav ◽  
J. Jussif ◽  
J. Alley ◽  
S. Lathwal ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
T Cell ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Cell Function ◽  
Immune Cell ◽  
Transcriptomic Profiling ◽  
Human T Cell

AbstractThe targeting of metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. In this study, carbon tracing and systems biology approaches integrating metabolomic and transcriptomic profiling data were used to identify adaptations in human T cell metabolism important for fueling pro-inflammatory T cell function. Results of this study demonstrate that T cell receptor (TCR) stimulation leads to a significant increase in glucose and amino acid metabolism that trigger downstream biosynthetic processes. Specifically, increased expression of several enzymes such as CTPS1, IL4I1, and ASL results in the reprogramming of amino acid metabolism. Additionally, the strength of TCR signaling resulted in different metabolic enzymes utilized by T cells to facilitate similar biochemical endpoints. Furthermore, this study shows that cyclosporine represses the pathways involved in amino acid and glucose metabolism, providing novel insights on the immunosuppressive mechanisms of this drug. To explore the implications of the findings of this study in clinical settings, conventional immunosuppressants were tested in combination with drugs that target metabolic pathways. Results showed that such combinations increased efficacy of conventional immunosuppressants. Overall, the results of this study provide a comprehensive resource for identifying metabolic targets for novel combinatorial regimens in the treatment of intractable immune diseases.

BIOCHEMICAL STUDIES OF AN UNNATURAL AND ANTITUMOR AMINO ACID: 1-AMINOCYCLOPENTANECARBOXYLIC ACID: II. EFFECTS ON CELLULAR RESPIRATION AND AMINO ACID METABOLISM

1962 ◽  
Vol 40 (4) ◽  
pp. 433-436 ◽  
Author(s):  
L. Berlinguet ◽  
Nicole Bégin ◽  
L. M. Babineau ◽  
R. O. Laferté
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Radioactive Substance ◽  
Cellular Respiration ◽  
Rat Tissues ◽  
Metabolic Products ◽  
Biochemical Studies

1-Aminocyclopentanecarboxylic acid (ACPC) was studied for its effect on cellular respiration of rat tissues and for its reactivity towards decarboxylases, transaminases, and amino acid oxidases. In the tissues studied, cellular respiration was normal. The amino acid was not decarboxylated, transaminated, or oxidized. The transamination and oxidation of other amino acids remained normal even in the presence of ACPC.Using the radioactive substance, it was found that the molecule remains intact within the cells since no metabolic products could be detected.

scholarly journals Identification of differentially expressed genes involved in amino acid and lipid accumulation of winter turnip rape (Brassica rapa L.) in response to cold stress

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245494
Author(s):  
Yan Fang ◽  
Jeffrey A. Coulter ◽  
Junyan Wu ◽  
Lijun Liu ◽  
Xuecai Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Cold Stress ◽  
Cold Tolerance ◽  
Brassica Rapa ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Differentially Expressed ◽  
Serine Acetyltransferase ◽  
Turnip Rape

Winter turnip rape (Brassica rapa L.) is an important overwintering oil crop that is widely planted in northwestern China. It considered to be a good genetic resource for cold-tolerant research because its roots can survive harsh winter conditions. Here, we performed comparative transcriptomics analysis of the roots of two winter turnip rape varieties, Longyou7 (L7, strong cold tolerance) and Tianyou2 (T2, low cold tolerance), under normal condition (CK) and cold stress (CT) condition. A total of 8,366 differentially expressed genes (DEGs) were detected between the two L7 root groups (L7CK_VS_L7CT), and 8,106 DEGs were detected for T2CK_VS_T2CT. Among the DEGs, two ω-3 fatty acid desaturase (FAD3), two delta-9 acyl-lipid desaturase 2 (ADS2), one diacylglycerol kinase (DGK), and one 3-ketoacyl-CoA synthase 2 (KCS2) were differentially expressed in the two varieties and identified to be related to fatty acid synthesis. Four glutamine synthetase cytosolic isozymes (GLN), serine acetyltransferase 1 (SAT1), and serine acetyltransferase 3 (SAT3) were down-regulated under cold stress, while S-adenosylmethionine decarboxylase proenzyme 1 (AMD1) had an up-regulation tendency in response to cold stress in the two samples. Moreover, the delta-1-pyrroline-5-carboxylate synthase (P5CS), δ-ornithine aminotransferase (δ-OAT), alanine-glyoxylate transaminase (AGXT), branched-chain-amino-acid transaminase (ilvE), alpha-aminoadipic semialdehyde synthase (AASS), Tyrosine aminotransferase (TAT) and arginine decarboxylase related to amino acid metabolism were identified in two cultivars variously expressed under cold stress. The above DEGs related to amino acid metabolism were suspected to the reason for amino acids content change. The RNA-seq data were validated by real-time quantitative RT-PCR of 19 randomly selected genes. The findings of our study provide the gene expression profile between two varieties of winter turnip rape, which lay the foundation for a deeper understanding of the highly complex regulatory mechanisms in plants during cold treatment.

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