1H-NMR-based metabonomic analysis of metabolic profiling in diabetic nephropathy rats induced by streptozotocin

2011 ◽  
Vol 300 (4) ◽  
pp. F947-F956 ◽  
Author(s):  
Liangcai Zhao ◽  
Hongchang Gao ◽  
Fulin Lian ◽  
Xia Liu ◽  
Yongxiang Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Metabolic Profiling ◽  
Ketone Body ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Metabolic Changes ◽  
Control Group ◽  
Acid Cycle ◽  
Pattern Recognition Analysis ◽  
Pathogenic Process

Elucidation of the metabolic profiling in diabetic nephropathy (DN) rats is of great assistance for understanding the pathogenesis of DN. In this study, 1H-nuclear magnetic resonance (NMR)-based metabonomics combined with HPLC measurements was used to quantitatively analyze the metabolic changes in urine and kidney extracts from diabetic 2-wk and 8-wk rats induced by streptozotocin (STZ). Pattern recognition analysis of either urine or kidney extracts indicated that the two diabetic groups were separated obviously from the control group, suggesting that the metabolic profiles of the diabetic groups were markedly different from the control. The diabetic 8-wk rats showed lower levels of creatine, dimethylamine, and higher levels of ascorbate, succinate, lactate, citrate, allantoin, 2-ketoglutarate, and 3-hydrobutyrate (3-HB) in the urine samples. Moreover, the diabetic 8-wk rats displayed lower levels of succinate, creatine, myo-inositol, alanine, lactate, and ATP, and higher levels of 3-HB and glucose in the kidney extracts. The observed metabolic changes imply the enhanced pathways of either lipid or ketone body synthesis and decreased pathways of either tricarboxylic acid cycle or glycolysis in DN rats compared with the control. Our results suggest that the energy metabolic changes are associated with the pathogenic process of DN.

scholarly journals Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yiyong Wei ◽  
Donghang Zhang ◽  
Jin Liu ◽  
Mengchan Ou ◽  
Peng Liang ◽  
...  
Keyword(s):  
Abdominal Surgery ◽  
General Anesthesia ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Metabolic Changes ◽  
Sevoflurane Anesthesia ◽  
Glutamate Metabolism ◽  
Acid Cycle ◽  
Link Type ◽  
The Mean

Abstract Background Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. Methods Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean − SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. Results The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. Conclusions Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. Trial registration www.chictr.org.cn. identifier: ChiCTR1800014327.

scholarly journals Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

Open Biology ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 150155 ◽  
Author(s):  
Vera Slaninova ◽  
Michaela Krafcikova ◽  
Raquel Perez-Gomez ◽  
Pavel Steffal ◽  
Lukas Trantirek ◽  
...  
Keyword(s):  
Warburg Effect ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Notch Signalling ◽  
Metabolic Changes ◽  
Acid Cycle ◽  
Notch Activity ◽  
Metabolic Genes ◽  
Direct Regulation ◽  
The Warburg Effect

Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo . Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.

scholarly journals Metabolic changes in the lymphocytes during influenza

2012 ◽  
Vol 93 (4) ◽  
pp. 580-584
Author(s):  
I V Sergeeva ◽  
N I Kamzalakova ◽  
E P Tikhonova ◽  
G V Bulygin
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Tricarboxylic Acid Cycle ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Tricarboxylic Acid ◽  
Nicotinamide Adenine ◽  
Control Group ◽  
Healthy Individuals ◽  
Acid Cycle ◽  
Intracellular Enzymes ◽  
Glucose 6 Phosphate Dehydrogenase

Aim. To assess the nature and intensity of metabolic processes in lymphocytes of patients with influenza according to the activity of intracellular enzymes in comparison to the severity of the disease. Methods. Determined were the enzymatic parameters of lymphocytes of 45 patients aged 18 to 42 years with a diagnosis of «influenza». Two groups of patients were formed: with moderate (24 patients) and severe (21 patients) course of the disease. Used as controls were the values the activity of intracellular enzymes of lymphocytes of 37 practically healthy individuals of comparable age. Results. In patients with a moderately severe course of the influenza compared with the controls noted was a significant increase in activity of glucose-6-phosphate dehydrogenase (3.17±0.53 and 2.74±0.31 mkE/10 000 cells, p 0.05) and glycerol-3-phosphate dehydrogenase (57.33±±5.65 and 0.84±0.16 mkE/10 000 cells respectively, p 0.001). The activity of lactate dehydrogenase was lower in patients than in controls (0.40±0.08 and 0.84±0.08 mkE/10 000 cells respectively, p 0.001). Indicators of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate dependant isocitrate dehydrogenases in lymphocytes of patients were lower than in the controls: the first indicator in the patients was 0.17±0.02 mkE/10 000 cells, in controls - 1.95±0.25 mkE/10 000 cells (p 0.001), and for the second indicator these values were respectively 0.09±0.01 and 31.02±±2.20 mkE/10 000 cells (p 0.001). In patients with a moderately severe course of influenza the activity of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate dependant glutamate dehydrogenases was significantly higher compared with healthy individuals: 63.67±5.32 and 0.34±0.06 mkE/10 000 cells, 1.45±0.18 and 0.11±0.02 mkE/10 000 cells respectively (p 0.001). The activity of nicotinamide adenine dinucleotide dependant malate dehydrogenase in patients was equal to 86.46±12.30 mkE/10 000 cells (in the control group 84.16±13.70 mkE/10 000 cells), and the activity of nicotinamide adenine dinucleotide phosphate dependant malate dehydrogenase was equal to 1.34±±0.25 mkE/10 000 cells (in the control group 0.33±0.07 mkE/10 000 cells, p 0.001). The activity of glutathione reductase was also higher in patients with the moderately severe course of the influenza: 5.86±0.25 mkE/10 000 cells, while the value in healthy individuals was 1.28±0.30 mkE/10 000 cells (p 0.001). In the group of patients with a severe course of influenza the activity of almost all (except for glucose-6-phosphate dehydrogenase) enzymes was higher than during the moderately severe course of disease. Conclusion. At the peak of the diseases noted were opposite changes in the activity of reactions of the pentose phosphate cycle and glycolysis. With a high functional load on the cells there is a significant reduction in the intensity of the reactions of the initial phase of the tricarboxylic acid cycle, which reduces the energy efficiency of the cycle, while the intense influx of metabolites to supply the tricarboxylic acid cycle with substrates of the amino acid metabolism provides enhanced transport of amino acids into the lymphocytes.

Characterization of urinary biomarkers and their relevant mechanisms of zoledronate-induced nephrotoxicity using rats and HK-2 cells

2019 ◽  
Vol 38 (5) ◽  
pp. 598-609
Author(s):  
Z Lan ◽  
K Chai ◽  
Y Jiang ◽  
X Liu
Keyword(s):  
Oxidative Stress ◽  
Tricarboxylic Acid Cycle ◽  
Kidney Injury ◽  
Urinary Metabolites ◽  
Tricarboxylic Acid ◽  
Glutathione Metabolism ◽  
Control Group ◽  
Acid Cycle ◽  
Urinary Levels ◽  
Group 3

The aim of this study was to identify biomarkers of zoledronate-induced nephrotoxicity and to further characterize the mechanisms underlying this process by analyzing urinary metabolites. Twenty-four rats were randomly divided into four groups containing four (two control groups) or eight rats (two zoledronate groups) per group. The rats were injected intravenously with saline or zoledronate (3 mg/kg) singly (single, 3 weeks) or repeatedly eight times (3 weeks/time, 24 weeks). Serum blood urea nitrogen, serum creatinine, creatinine clearance, and kidney injury observed by hematoxylin and eosin and immunohistochemical staining were changed only in the repeated zoledronate group (3 mg/kg, 3 weeks/time, 24 weeks). Urinary levels of S-adenosylmethionine, S-adenosylhomocysteine, l-cystathionine, l-γ-glutamylcysteine, and glutathione related to glutathione metabolism and fumaric acid and succinic acid related to the tricarboxylic acid cycle in the zoledronate-treated group (3 mg/kg, 3 weeks/time, 24 weeks) were significantly lower than those in the control group, suggesting that zoledronate may cause cellular oxidative stress. Besides, urinary levels of uracil and uridine related to pyrimidine metabolism also decreased after zoledronate treatment (3 mg/kg, 3 weeks/time, 24 weeks), while the levels of hypoxanthine related to purine metabolism, histamine related to histamine metabolism, and several amino acids were significantly increased. Moreover, zoledronate-induced enhanced oxidative stress and histamine overproduction were confirmed by reactive oxygen species (ROS) and histamine measurement in a human proximal tubular cell line. Taken together, zoledronate-induced nephrotoxicity may be attributed to it inducing perturbations in glutathione biosynthesis and the tricarboxylic acid cycle, further causing ROS overproduction, oxidative stress, and cellular inflammation, thereby leading to nephrotoxicity.

scholarly journals Maximum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone-body and glutamine utilization pathways in lymphocytes of the rat

1982 ◽  
Vol 208 (3) ◽  
pp. 743-748 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Eric A. Newsholme
Keyword(s):  
Ketone Body ◽  
Citrate Synthase ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Maximum Activity ◽  
Graft Versus Host Reaction ◽  
Acid Cycle ◽  
Oxoglutarate Dehydrogenase

1. The maximum activity of hexokinase in lymphocytes is similar to that of 6-phosphofructokinase, but considerably greater than that of phosphorylase, suggesting that glucose rather than glycogen is the major carbohydrate fuel for these cells. Starvation increased slightly the activities of some of the glycolytic enzymes. A local immunological challenge in vivo (a graft-versus-host reaction) increased the activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and lactate dehydrogenase, confirming the importance of the glycolytic pathway in cell division. 2. The activities of the ketone-body-utilizing enzymes were lower than those of hexokinase or 6-phosphofructokinase, unlike in muscle and brain, and were not affected by starvation. It is suggested that the ketone bodies will not provide a quantitatively important alternative fuel to glucose in lymphocytes. 3. Of the enzymes of the tricarboxylic acid cycle whose activities were measured, that of oxoglutarate dehydrogenase was the lowest, yet its activity (about 4.0μmol/min per g dry wt. at 37°C) was considerably greater than the flux through the cycle (0.5μmol/min per g calculated from oxygen consumption by incubated lymphocytes). The activity was decreased by starvation, but that of citrate synthase was increased by the local immunological challenge in vivo. It is suggested that the rate of the cycle would increase towards the capacity indicated by oxoglutarate dehydrogenase in proliferating lymphocytes. 4. Enzymes possibly involved in the pathway of glutamine oxidation were measured in lymphocytes, which suggests that an aminotransferase reaction(s) (probably aspartate aminotransferase) is important in the conversion of glutamate into oxoglutarate rather than glutamate dehydrogenase, and that the maximum activity of glutaminase is markedly in excess of the rate of glutamine utilization by incubated lymphocytes. The activity of glutaminase is increased by both starvation and the local immunological challenge in vivo. This last finding suggests that metabolism of glutamine via glutaminase is important in proliferating lymphocytes.

scholarly journals Effects of Moxibustion and Moxa Smoke on Behavior Changes and Energy Metabolism in APP/PS1 Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Lue Ha ◽  
Mengyun Yu ◽  
Zhiyi Yan ◽  
Zhang Rui ◽  
Baixiao Zhao
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Negative Control ◽  
Control Group ◽  
Behavioral Tests ◽  
Acid Cycle ◽  
Moxibustion Group ◽  
Model Control

Objective. To investigate the antiaging effects of moxibustion and moxa smoke on APP/PS1 mice and to illustrate the mechanism of moxibustion improving Alzheimer’s disease (AD). Methods. 36 male APP/PS1 mice were randomly assigned into three groups (n = 12), including a model control group, a moxibustion group, and a moxa smoke group. In addition, 12 C57BL/6 normal mice served as a normal (negative) control group. Mice in the moxibustion group received moxibustion intervention using Guanyuan (RN4) acupoint. Mice in the moxa smoke group received moxa smoke exposure with the same frequency as the moxibustion group. Behavioral tests were implemented in the 9th week, 3 days after the completion of the intervention. Tricarboxylic acid cycle and fatty acid metabolomics assessments of the mice were determined after behavioral tests. Results. In this study, relative to normal mice, we found that AD mice showed altered tricarboxylic and fatty acid metabolism and showed behavioral changes consistent with the onset of AD. However, both the moxibustion and moxa smoke interventions were able to mitigate these effects to some degree in AD mice. Conclusions. The data suggest that tricarboxylic acid cycle and unsaturated fatty acid metabolomics changes may be a target of AD, and the beneficial effects of moxibustion on cognitive behaviors may be mediated by the energy metabolism system.

scholarly journals Inhibition of cancer metabolism: a patent landscape

2019 ◽  
Vol 8 (4) ◽  
pp. 117-138 ◽  
Author(s):  
William P Katt ◽  
Richard A Cerione
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Small Molecule ◽  
Cancer Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Metabolic Changes ◽  
Pharmacological Intervention ◽  
Acid Cycle ◽  
Patent Landscape

Cancer metabolism is currently a hot topic. Since it was first realized that cancer cells rely upon an altered metabolic program to sustain their rapid proliferation, the enzymes that support those metabolic changes have appeared to be good targets for pharmacological intervention. Here, we discuss efforts pertaining to targets in cancer metabolism, focusing upon the tricarboxylic acid cycle and the mechanisms which feed nutrients into it. We describe a broad landscape of small-molecule inhibitors, targeting a dozen different proteins, each implicated in cancer progression. We hope that this will serve as a reference both to the areas being most highly examined today and, relatedly, the areas that are still ripe for novel intervention.

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