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

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.

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The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽

10.3390/cancers11050675 ◽

2019 ◽

Vol 11 (5) ◽

pp. 675 ◽

Cited By ~ 25

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.

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

10.21203/rs.3.rs-526582/v1 ◽

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.

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Dietary Concentrate Supplementation Alters Serum Metabolic Profiles Related to Energy and Amino Acid Metabolism in Grazing Simmental Heifers

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.743410 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hao Chen ◽

Chunjie Wang ◽

Simujide Huasai ◽

Aorigele Chen

Keyword(s):

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Average Daily Gain ◽

Enrichment Analysis ◽

Growth Potential ◽

Final Body Weight ◽

Serum Metabolites ◽

Concentrate Supplementation ◽

Altered Glucose

Supplementation plays a vital role in the growth performance of grazing heifers. We investigated the effects of maize-based concentrate supplementation on the serum metabolome in grazing heifers. Twenty-four 7-month-old heifers (211.65 ± 4.25 kg BW) were randomly divided into a supplement (SUP) group and a control (CON) group. The results indicated that concentrate supplementation increased the final body weight (BW) of grazing heifers, and the average daily gain (ADG) was 61.5% (P = 0.011) higher in the SUP group than in the CON group. Serum concentrations of total protein (TP), triglyceride (TG), and leptin were higher in the SUP group than in the CON group (p < 0.05). Supplementation increased serum metabolites and amino acids and markedly altered glucose, lipid, and protein metabolism, which contributed to the heifer growth. Furthermore, by multivariate analysis, 45 serum metabolites were identified as significantly different between the two groups. Enrichment analysis revealed that arginine biosynthesis and tryptophan metabolism as well as glycerophospholipid metabolism were significantly enriched between the two groups. We concluded that the growth potential of heifers could be improved by maize-based concentrate supplementation, and the main biological pathways affected were those related to energy and amino acid metabolism.

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

Frontiers in Microbiology ◽

10.3389/fmicb.2021.740482 ◽

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.

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Elucidation of salt stress defense and tolerance mechanisms of marine red yeast Sporobolomyces pararoseus NGR using transcriptomic and metabolomic profiling

10.7287/peerj.preprints.27823v1 ◽

2019 ◽

Author(s):

Chunji Li ◽

Die Zhao ◽

Ning Zhang ◽

Bingxue Li

Keyword(s):

Salt Stress ◽

Lipid Metabolism ◽

Amino Acid ◽

Network Analysis ◽

Transcriptome Analysis ◽

Metabolic Profiling ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Salt Tolerant ◽

Tolerance Mechanisms

Background. Salinity stress is one of the most environmental stresses in agricultural regions worldwide. Salinity inhibits shoot and root growth of various crops, which culminate in reductions in the quality and yield. It is of crucial to understand the molecular biological mechanisms of salt stress responses and defenses in order to enhance crops salt-tolerance. Sporobolomyces pararoseus is a member of marine red yeasts. Since marine red yeast has been naturally selected for its long-term survival in high-salt marine ecosystems, some unique salt-tolerant mechanism has been developed. Little research has conducted so far by considering S. pararoseus as model microorganisms to study salt stress tolerance mechanisms. A better understanding of the mechanisms mediating salt stress of S. pararoseus NGR will provide valuable information for enhancing the crops salt-tolerant via genetic engineering. Methods. S. pararoseus NGR (CGMCC 2.5280) cultures were treated with initial NaCl concentrations of 0.75 M throughout 3 days of growth period. Transcriptome analysis was performed using RNA-seq to study the differentially expressed genes (DEGs) between the NaCl-treated cells and the control cells. Metabolome analysis was performed using the LC-MS/MS untargeted metabolic profiling to study the differentially accumulated metabolites between the NaCl-treated cells and the control cells. Co-expression network analysis was carried out using the screening parameters of correlation coefficient = 0.99 and p-value = 0.01. Transcriptome analysis results were confirmed by real-time quantitative PCR (RT-qPCR). Results. After sequencing, de novo assembly and quantitative assessment, 9,533 unigenes were finally generated with an average length of 1,538 bp. A total of 3,849 DGEs were identified in NaCl-treated cultures, including 2,019 up-regulated genes and 1,830 down-regulated genes. Screening of metabolite features with untargeted metabolic profiling of all samples in NaCl-treated and control group, we characterized 4,862 compounds from the LC–MS/MS-based dataset. An integrated analysis of transcriptome and metabolome indicated that amino acid metabolism, carbohydrate metabolism, and lipid metabolism is significantly enriched in response to salt stress. Co-expression network analysis showed that 28 genes and 8 metabolites played an important role in the response of S. pararoseus NGR and defense against salt stress, which provides valuable clues for subsequent validation. Together, our results suggested that the most primary salt-tolerant mechanism of the S. pararoseus NGR is the biosynthesis of carotenoids, and torulene showed the dominated effect among them. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism act as its secondary salt-tolerant mechanism.

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

10.1101/635789 ◽

2019 ◽

Cited By ~ 1

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.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4115 ◽

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

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Comparative Proteomic Analysis of Leaves at Different Ages in Allotriploid Populus

Forests ◽

10.3390/f11111154 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1154

Author(s):

Jiang Li ◽

Yi Wang ◽

Hairong Wei ◽

Xiangyang Kang

Keyword(s):

Amino Acid ◽

Carbon Metabolism ◽

Proteomic Analysis ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Leaf Age ◽

Enrichment Analysis ◽

C1 Metabolism ◽

Comparative Proteomic Analysis ◽

N Metabolism

Triploid poplar trees have been shown to have a number of growth advantages, especially much bigger leaves that contribute greatly to the increased biomass. In this study, we focused on the relationships between leaf age and leaf metabolism in triploids. We performed comparative proteomic analysis of the 5th (FDR5), 10th (FDR10), and 25th (FDR25) leaves from the apical meristems in allotriploids originated from first-division restitution (FDR). A total of 1970, 1916, and 1850 proteins were identified in the FDR5, FDR10, and FDR25, respectively. Principle component analysis (PCA) and differentially accumulated protein (DAP) analysis showed that FDR10 and FDR25 displayed higher similarities of protein accumulation patterns as compared to FDR5. MapMan enrichment analysis showed that several primary metabolic pathways or processes were significantly enriched in the DAPs. For example, photosynthesis, major CHO metabolism, glycolysis, N metabolism, redox, C1-metabolism, DNA, and protein turnover were significantly altered in both FDR10 and FDR25 compared with FDR5. In addition, amino acid metabolism and gluconeogenesis/glyoxylate cycle also underwent significant changes in FDR25 compared with FDR5. However, only amino acid metabolism was significantly enriched in the DAPs between FDR25 and FDR10. Further, DAP accumulation pattern analysis implied that FDR5, FDR10, and FDR25 were placed in the young, mature, and primary senescence stages of leaves. The most DAPs involved in the light reaction, photorespiration, Calvin cycle, starch and sucrose metabolism, pentose phosphate pathway (OPP), tricarboxylic acid (TCA) cycle, N metabolism, and C1-metabolism displayed higher accumulation in both FDR10 and FDR25 compared to FDR5. However, the most DAPs that are involved in cell wall and lipid metabolism, tetrapyrrole synthesis, nucleotide metabolism exhibited lower accumulation in both FDR10 and FDR25. Almost all DAPs between FDR-10 and FDR-25 showed a dramatic decrease in FDR25. KEGG enrichment analysis showed that carbon metabolism was altered significantly at different leaf ages. DAPs that are involved in carbon metabolism were predicted as different points in protein–protein interaction (PPI) networks from the STRING database. Finally, inconsistent transcript and protein abundance was found for DAPs, indicating the presence of posttranscriptional regulation during leaf-age progression process.

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Elucidation of salt stress defense and tolerance mechanisms of marine red yeast Sporobolomyces pararoseus NGR using transcriptomic and metabolomic profiling

10.7287/peerj.preprints.27823 ◽

2019 ◽

Author(s):

Chunji Li ◽

Die Zhao ◽

Ning Zhang ◽

Bingxue Li

Keyword(s):

Salt Stress ◽

Lipid Metabolism ◽

Amino Acid ◽

Network Analysis ◽

Transcriptome Analysis ◽

Metabolic Profiling ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Salt Tolerant ◽

Tolerance Mechanisms

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Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

PeerJ ◽

10.7717/peerj.1399 ◽

2015 ◽

Vol 3 ◽

pp. e1399 ◽

Cited By ~ 5

Author(s):

Sofía Arriarán ◽

Silvia Agnelli ◽

Xavier Remesar ◽

José Antonio Fernández-López ◽

Marià Alemany

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Amino Acid ◽

White Adipose Tissue ◽

Metabolic Pathways ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Urea Cycle ◽

Adipose Organ ◽

Expression And Activity

Background and Objectives.White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism.Experimental Design.Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities.Results.There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT.Conclusions.We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole.

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