scholarly journals Metabolomic Analysis of Differential Changes in Metabolites during ATP Oscillations in Chondrogenesis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hyuck Joon Kwon ◽  
Yoshihiro Ohmiya

Prechondrogenic condensation is a critical step for skeletal pattern formation. Recent studies reported that ATP oscillations play an essential role in prechondrogenic condensation. However, the molecular mechanism to underlie ATP oscillations remains poorly understood. In the present study, it was investigated how changes in metabolites are implicated in ATP oscillations during chondrogenesis by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). CE-TOF-MS detected 93 cationic and 109 anionic compounds derived from known metabolic pathways. 15 cationic and 18 anionic compounds revealed significant change between peak and trough of ATP oscillations. These results implicate that glycolysis, mitochondrial respiration and uronic acid pathway oscillate in phase with ATP oscillations, while PPRP and nucleotides synthesis pathways oscillate in antiphase with ATP oscillations. This suggests that the ATP-producing glycolysis and mitochondrial respiration oscillate in antiphase with the ATP-consuming PPRP/nucleotide synthesis pathway during chondrogenesis.

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yujie Gong ◽  
Wentao Lyu ◽  
Xingfen Shi ◽  
Xiaoting Zou ◽  
Lizhi Lu ◽  
...  

During the process of fatty liver production by overfeeding, the levels of endogenous metabolites in the serum of geese would change dramatically. This study investigated the effects of overfeeding on serum metabolism of Landes geese and the underlying mechanisms using a metabolomics approach. Sixty Landes geese of the same age were randomly divided into the following three groups with 20 replicates in each group: D0 group (free from gavage); D7 group (overfeeding for 7 days); D25 group (overfeeding for 25 days). At the end of the experiment, 10 geese of similar weight from each group were selected for slaughter and sampling. The results showed that overfeeding significantly increased the body weight and the liver weight of geese. Serum enzymatic activities and serum lipid levels were significantly enhanced following overfeeding. Gas chromatography time-of-flight/mass spectrometry (GC-TOF/MS) was employed to explore the serum metabolic patterns, and to identify potential contributors to the formation of fatty liver and the correlated metabolic pathways. Relative to overfeeding for 7 days, a large number of endogenous molecules in serum of geese overfed for 25 days were altered. Continuous elevated levels of pyruvic acid, alanine, proline and beta-glycerophosphoric acid and reduced lactic acid level were observed in the serum of overfed geese. Pathway exploration found that the most of significantly different metabolites were involved in amino acids, carbohydrate and lipid metabolism. The present study exhibited the efficient capability of Landes geese to produce fatty liver, identified potential biomarkers and disturbed metabolic pathways in liver steatosis. These findings might reveal the underlying mechanisms of fatty liver formation and provide some theoretical basis for the diagnosis and treatment of liver diseases.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shaowa Lü ◽  
Mingtao Zhu ◽  
Qiaoxin Guo ◽  
Dan Xu ◽  
Yuyan Guo ◽  
...  

Rheumatoid arthritis (RA) is a chronic autoimmune disease with high incidence and high disability and recurrence rates. Caulophyllum robustum Maxim (C. robustum) is a traditional Chinese medicine (TCM) with main effective parts (CRME) commonly used for RA treatment. To explore the mechanism of CRME in RA, we used metabolomics to investigate the effect of CRME intervention on urine metabolism in rats with collagen-induced arthritis (CIA). CIA rats were randomly divided into normal control, CIA model, and CRME groups. A metabolomics approach, using Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry, was developed to perform urinary metabolic profiling. Differential metabolites were identified by comparing the CIA model and CRME groups. Preliminarily, 56 significant differential metabolites were identified in urine, and 20 metabolic pathways were disturbed by the CIA. The amount of 16 different metabolites changed in urine after CRME intervention. The production of these metabolites involves tryptophan, tyrosine, energy, cholesterol, and vitamin metabolism. CRME has anti-inflammatory and immunosuppressive effects in CIA model rats. By examining the endogenous metabolite levels, we identified potential CRME targets and pathways involved in the treatment of RA. The results of our metabolic studies indicate that CRME regulates amino acid, vitamin, energy, and lipid metabolism pathways to treat RA and may provide a new explanation for the anti-RA mechanism of CRME.


2018 ◽  
Vol 5 (10) ◽  
pp. 180759
Author(s):  
L. J. Zhu ◽  
S. S. Sun ◽  
Y. X. Hu ◽  
Y. F. Liu

To explore metabolism mechanism of paeoniflorin in the liver and further understand intact metabolism process of paeoniflorin, a rapid, convenient and effective assay is described using ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). The strategy was confirmed in the following primary processes: firstly, different concentration of paeoniflorin, rat liver microsomes, coenzymes and different incubated conditions were optimized to build a biotransformation model of rat liver microsomes in vitro by high performance liquid chromatography with diode array detection (HPLC-DAD); secondly, the metabolites of paeoniflorin in rat liver microsomes were detected and screened using UPLC-Q-TOF-MS/MS by comparing the total ion chromatogram (TIC) of the experimental group with those of control groups; finally, the molecular formulae and corresponding chemical structures of paeoniflorin metabolites were identified by comparing the MS and MS/MS spectra with the self-constructed database and simulation software. Based on this analytical strategy, 20 metabolites of paeoniflorin were found and 6 metabolites (including four new compounds) were tentatively identified. It was shown that hydrolysis and oxidation were the major metabolic pathways of paeoniflorin in rat liver microsomes, and the main metabolic sites were the structures of pinane and the ester bond. These findings were significant for a better understanding of the metabolism of paeoniflorin in rat liver microsomes and the proposed metabolic pathways of paeoniflorin might provide fundamental support for the further research in the pharmacological mechanism of Paeoniae Radix Rubra (PRR).


Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 161 ◽  
Author(s):  
Ruinan Yang ◽  
Ligang Deng ◽  
Liangxiao Zhang ◽  
Xiaofeng Yue ◽  
Jin Mao ◽  
...  

Rapeseed is an important oilseed with proper fatty acid composition and abundant bioactive components. Canada and China are the two major rapeseed-producing countries all over the world. Meanwhile, Canada and Mongolia are major importers of rapeseed due to the great demand for rapeseed in China. To investigate the metabolites in rapeseeds from three countries, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics was employed to analyze rapeseeds from China, Canada, and Mongolia. As results, 67, 53, and 68 metabolites showed significant differences between Chinese and Canadian, Chinese and Mongolian, and Canadian and Mongolian rapeseeds, respectively. Differential metabolites were mainly distributed in the metabolic pathways including phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, and ubiquinone and other terpenoid-quinone biosynthesis. Among the differential metabolites, contents of sinapate and sinapine were higher in Chinese rapeseeds, while the contents of brassicasterol, stigmasterol, and campestanol were higher in Canadian rapeseeds. These findings might provide insight into the metabolic characteristics of rapeseeds from three countries to guide processing and consumption of the products of rapeseed.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Sijiang Liu ◽  
Zhaojin Yu

In this study, The metabolites, metabolic pathways, and metabolic fragmentation mode of a tyrosine kinase inhibitor- (TKI-) imatinib in rats were investigated. The samples for analysis were pretreated via solid-phase extraction, and the metabolism of imatinib in rats was studied using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Eighteen imatinib metabolites were identified in rat plasma, 21 in bile, 18 in urine, and 12 in feces. Twenty-seven of the above compounds were confirmed as metabolites of imatinib and 9 of them were newly discovered for the first time. Oxidation, hydroxylation, dealkylation, and catalytic dehydrogenation are the main metabolic pathways in phase I. For phase II, the main metabolic pathways were N-acetylation, methylation, cysteine, and glucuronidation binding. The fragment ions of imatinib and its metabolites were confirmed to be produced by the cleavage of the C-N bond at the amide bond. The newly discovered metabolite of imatinib was identified by UHPLC-Q-TOF-MS/MS. The metabolic pathway of imatinib and its fragmentation pattern were summarized. These results could be helpful to study the safety of imatinib for clinical use.


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