scholarly journals Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic Signatures

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1242
Author(s):  
Daniela Bispo ◽  
Victoria Fabris ◽  
Caroline A. Lamb ◽  
Claudia Lanari ◽  
Luisa A. Helguero ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Metastatic Breast ◽  
Atp Synthesis ◽  
Metastatic Potential ◽  
Polar Compounds ◽  
Phospholipid Metabolism ◽  
Nucleotide Metabolism ◽  
Nmr Metabolomics ◽  
Metabolic Signatures

The metabolic characteristics of metastatic and non-metastatic breast carcinomas remain poorly studied. In this work, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was used to compare two medroxyprogesterone acetate (MPA)-induced mammary carcinomas lines with different metastatic abilities. Different metabolic signatures distinguished the non-metastatic (59-2-HI) and the metastatic (C7-2-HI) lines, with glucose, amino acid metabolism, nucleotide metabolism and lipid metabolism as the major affected pathways. Non-metastatic tumours appeared to be characterised by: (a) reduced glycolysis and tricarboxylic acid cycle (TCA) activities, possibly resulting in slower NADH biosynthesis and reduced mitochondrial transport chain activity and ATP synthesis; (b) glutamate accumulation possibly related to reduced glutathione activity and reduced mTORC1 activity; and (c) a clear shift to lower phosphoscholine/glycerophosphocholine ratios and sphingomyelin levels. Within each tumour line, metabolic profiles also differed significantly between tumours (i.e., mice). Metastatic tumours exhibited marked inter-tumour changes in polar compounds, some suggesting different glycolytic capacities. Such tumours also showed larger intra-tumour variations in metabolites involved in nucleotide and cholesterol/fatty acid metabolism, in tandem with less changes in TCA and phospholipid metabolism, compared to non-metastatic tumours. This study shows the valuable contribution of untargeted NMR metabolomics to characterise tumour metabolism, thus opening enticing opportunities to find metabolic markers related to metastatic ability in endocrine breast cancer.

scholarly journals Effect of Huangqin Tang on Urine Metabolic Profile in Rats with Ulcerative Colitis Based on UPLC-Q-Exactive Orbitrap MS

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dunfang Wang ◽  
Xuran Ma ◽  
Shanshan Guo ◽  
Yanli Wang ◽  
Tao Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fatty Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Unsaturated Fatty Acids ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Q Exactive ◽  
Therapeutic Mechanisms

As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.

scholarly journals Metabolic Profiling Revealed Dysregulated Arachidonic Acid Metabolism and Tryptophan Metabolism in the Lungs from Canines with Pacing-induced Heart Failure

2020 ◽  
Author(s):  
Junhan Zhao ◽  
Jing Wang ◽  
Shengwen Yang ◽  
Ran Jing ◽  
Xi Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Sham Group ◽  
Acid Metabolism ◽  
Congestion Management ◽  
Arachidonic Acid Metabolism ◽  
Tryptophan Metabolism ◽  
Negative Ion ◽  
Metabolic Signatures

Abstract Background: Lung has critical pathophysiological connections to heart and lung congestion presents one of the hallmark features of heart failure (HF). This study aimed to explore the metabolic signatures and disturbances in lungs under HF condition and provide insights on the pathophysiology of the lungs under HF condition from the perspective of metabolism.Methods: In this study, we established a rapid pacing induced HF canine model and applied a comprehensive untargeted metabolomics method to comparatively assessed the metabolomics profiles in the lung tissues from HF group and sham group. Results: Distinct metabolic signatures were identified in the lungs between beagles in HF group and sham group. 81 dysregulated metabolites were identified as differential metabolites (adjusted P <0.05, FC≥2 or≤0.5) in positive ion mode and 80 dysregulated metabolites in negative ion mode, indicating a profound metabolic alteration in the lungs under HF condition. In pathway analysis, arachidonic acid metabolism and tryptophan metabolism were identified as the most significant dysregulated metabolic pathways in the lungs from HF beagles.Conclusions: In this study, we identified profound metabolic variation and dysregulated metabolic pathways, which may deepen our understanding on the pathophysiology of the lungs under HF condition from the perspective of metabolism and open new avenues in lung congestion management in HF.

scholarly journals Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Dylan Gerard Ryan ◽  
Ming Yang ◽  
Hiran A Prag ◽  
Giovanny Rodriguez Blanco ◽  
Efterpi Nikitopoulou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Response ◽  
Tricarboxylic Acid Cycle ◽  
Fumarate Hydratase ◽  
Tca Cycle ◽  
Comparative Approach ◽  
Redox Biology ◽  
The Tca Cycle

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in murine kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis.

scholarly journals Forensic NMR metabolomics: one more arrow in the quiver

Metabolomics ◽  
2020 ◽  
Vol 16 (11) ◽  
Author(s):  
Emanuela Locci ◽  
Giovanni Bazzano ◽  
Alberto Chighine ◽  
Francesco Locco ◽  
Ernesto Ferraro ◽  
...  
Keyword(s):  
Drugs Of Abuse ◽  
Recent Literature ◽  
Metabolic Profiles ◽  
Time Since Death ◽  
Post Mortem ◽  
Nmr Metabolomics ◽  
Additional Information ◽  
Shed Light ◽  
Metabolic Signatures

Abstract Introduction NMR metabolomics is increasingly used in forensics, due to the possibility of investigating both endogenous metabolic profiles and exogenous molecules that may help to describe metabolic patterns and their modifications associated to specific conditions of forensic interest. Objectives The aim of this work was to review the recent literature and depict the information provided by NMR metabolomics. Attention has been devoted to the identification of peculiar metabolic signatures and specific ante-mortem and post-mortem profiles or biomarkers related to different conditions of forensic concern, such as the identification of biological traces, the estimation of the time since death, and the exposure to drugs of abuse. Results and Conclusion The results of the described studies highlight how forensics can benefit from NMR metabolomics by gaining additional information that may help to shed light in several forensic issues that still deserve to be further elucidated.

scholarly journals The effect of glucagon treatment and starvation of virgin and lactating rats on the rates of oxidation of octanoyl-l-carnitine and octanoate by isolated liver mitochondria

1980 ◽  
Vol 190 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Victor A. Zammit
Keyword(s):  
Fatty Acids ◽  
Tricarboxylic Acid Cycle ◽  
Atp Synthesis ◽  
Liver Mitochondria ◽  
Oxidation Rates ◽  
Consumption Rates ◽  
Mitochondrial Oxidation ◽  
Elevated Rate ◽  
Isolated Liver ◽  
Chain Fatty Acids

1. Oxygen-consumption rates owing to oxidation of octanoate or octanoylcarnitine by isolated mitochondria from livers of fed, starved and glucagon-treated virgin or 12-day-lactating animals were measured under State-3 and State-4 conditions, in the presence or absence of l-malate and inhibitors of tricarboxylic acid-cycle activity (malonate and fluorocitrate). 2. Mitochondria from fed lactating animals had a slightly lower rate of octanoylcarnitine oxidation than did those of fed virgin animals, whereas the rates of octanoate oxidation were unaffected. 3. Starvation of virgin animals for 24h or 48h resulted in a large (70–100%) increase in mitochondrial octanoylcarnitine oxidation; rates of octanoate oxidation were either unaffected (24 and 48h starvation in the absence of malonate and fluorocitrate) or diminished by 30% (48h starvation in the presence of inhibitors). In lactating animals, 24h starvation resulted in a smaller increase in the rate of octanoylcarnitine oxidation than that obtained for mitochondria from virgin rats. 4. Glucagon treatment (by intra-abdominal injection) of fed virgin and lactating rats increased the rate of mitochondrial oxidation of both octanoylcarnitine and octanoate. Injection of glucagon into 48h-starved virgin rats did not increase further the already elevated rate of octanoylcarnitine oxidation, but reversed the inhibition of octanoate β-oxidation observed for these mitochondria in the presence of malonate and fluorocitrate. 5. It is suggested that glucagon activates octanoylcarnitine oxidation by increasing the activity of the carnitine/acylcarnitine transport system [Parvin & Pande (1979) J. Biol. Chem.254, 5423–5429] and that the increase in octanoate oxidation by mitochondria from glucagon-treated animals is caused by the increased rate of ATP synthesis in these mitochondria. 6. The results are discussed in relation to the increased capacity of the liver to oxidize long-chain fatty acids and carnitine esters of medium-chain fatty acids under conditions characterized by increased ketogenesis.

scholarly journals Metabolomic Profiles of Bovine Mammary Epithelial Cells Stimulated by Lipopolysaccharide

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yixin Huang ◽  
Liuhong Shen ◽  
Jing Jiang ◽  
Qipin Xu ◽  
Zhengzhong Luo ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Linoleic Acid ◽  
Epithelial Cells ◽  
High Performance ◽  
Acid Metabolism ◽  
Mammary Epithelial Cells ◽  
Phospholipid Metabolism ◽  
Mammary Epithelial ◽  
Multivariate Statistical ◽  
Bovine Mammary Epithelial Cells

AbstractBovine mammary epithelial cells (bMECs) are the main cells of the dairy cow mammary gland. In addition to their role in milk production, they are effector cells of mammary immunity. However, there is little information about changes in metabolites of bMECs when stimulated by lipopolysaccharide (LPS). This study describes a metabolomics analysis of the LPS-stimulated bMECs to provide a basis for the identification of potential diagnostic screening biomarkers and possible treatments for bovine mammary gland inflammation. In the present study, bMECs were challenged with 500 ng/mL LPS and samples were taken at 0 h, 12 h and 24 h post stimulation. Metabolic changes were investigated using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS) with univariate and multivariate statistical analyses. Clustering and metabolic pathway changes were established by MetaboAnalyst. Sixty-three differential metabolites were identified, including glycerophosphocholine, glycerol-3-phosphate, L-carnitine, L-aspartate, glutathione, prostaglandin G2, α-linolenic acid and linoleic acid. They were mainly involved in eight pathways, including D-glutamine and D-glutamic acid metabolism; linoleic acid metabolism; α-linolenic metabolism; and phospholipid metabolism. The results suggest that bMECs are able to regulate pro-inflammatory, anti-inflammatory, antioxidation and energy-producing related metabolites through lipid, antioxidation and energy metabolism in response to inflammatory stimuli.

Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle

2001 ◽  
Vol 90 (3) ◽  
pp. 1137-1157 ◽  
Author(s):  
David A. Hood
Keyword(s):  
Transcription Factors ◽  
Respiratory Chain ◽  
Mitochondrial Biogenesis ◽  
Adenine Nucleotide ◽  
Contractile Activity ◽  
Recovery Period ◽  
Atp Synthesis ◽  
Nucleotide Metabolism ◽  
Significant Shift ◽  
Mrna Levels

Chronic contractile activity produces mitochondrial biogenesis in muscle. This adaptation results in a significant shift in adenine nucleotide metabolism, with attendant improvements in fatigue resistance. The vast majority of mitochondrial proteins are derived from the nuclear genome, necessitating the transcription of genes, the translation of mRNA into protein, the targeting of the protein to a mitochondrial compartment via the import machinery, and the assembly of multisubunit enzyme complexes in the respiratory chain or matrix. Putative signals involved in initiating this pathway of gene expression in response to contractile activity likely arise from combinations of accelerations in ATP turnover or imbalances between mitochondrial ATP synthesis and cellular ATP demand, and Ca2+ fluxes. These rapid events are followed by the activation of exercise-responsive kinases, which phosphorylate proteins such as transcription factors, which subsequently bind to upstream regulatory regions in DNA, to alter transcription rates. Contractile activity increases the mRNA levels of nuclear-encoded proteins such as cytochrome c and mitochondrial transcription factor A (Tfam) and mRNA levels of upstream transcription factors like c- junand nuclear respiratory factor-1 (NRF-1). mRNA level changes are often most evident during the postexercise recovery period, and they can occur as a result of contractile activity-induced increases in transcription or mRNA stability. Tfam is imported into mitochondria and controls the expression of mitochondrial DNA (mtDNA). mtDNA contributes only 13 protein products to the respiratory chain, but they are vital for electron transport and ATP synthesis. Contractile activity increases Tfam expression and accelerates its import into mitochondria, resulting in increased mtDNA transcription and replication. The result of this coordinated expression of the nuclear and the mitochondrial genomes, along with poorly understood changes in phospholipid synthesis, is an expansion of the muscle mitochondrial reticulum. Further understanding of 1) regulation of mtDNA expression, 2) upstream activators of NRF-1 and other transcription factors, 3) the identity of mRNA stabilizing proteins, and 4) potential of contractile activity-induced changes in apoptotic signals are warranted.

Development of a novel metastatic breast cancer score based on hyaluronic acid metabolism

2012 ◽  
Vol 30 (1) ◽  
Author(s):  
Hatem A. El-mezayen ◽  
El-Shahat A. Toson ◽  
Hossam Darwish ◽  
Fatheya M. Metwally
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Metastatic Breast Cancer ◽  
Acid Metabolism ◽  
Metastatic Breast

scholarly journals Gene expression in hypothalamus, liver, and adipose tissues and food intake response to melanocortin-4 receptor agonist in pigs expressing melanocortin-4 receptor mutations

2010 ◽  
Vol 41 (3) ◽  
pp. 254-268 ◽  
Author(s):  
C. Richard Barb ◽  
Gary J. Hausman ◽  
Romdhane Rekaya ◽  
Clay A. Lents ◽  
Sender Lkhagvadorj ◽  
...  
Keyword(s):  
Food Intake ◽  
Transcriptional Profiling ◽  
Cell Communication ◽  
Atp Synthesis ◽  
Acid Synthesis ◽  
Nucleotide Metabolism ◽  
Differentially Expressed ◽  
Metabolic Switch ◽  
Amino Acid Synthesis ◽  
Melanocortin 4 Receptor

Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular injection of melanocortin-4 receptor (MC4R) agonist [Nle4, d-Phe7]-α-melanocyte stimulating hormone (NDP-MSH) in pigs homozygous for the missense mutation in the MC4R, D298 allele ( n = 12), N298 allele ( n = 12), or heterozygous ( n = 12). Food intake (FI) was measured at 12 and 24 h after treatment. All pigs were killed at 24 h after treatment, and hypothalamus, liver, and back-fat tissue was collected. NDP-MSH suppressed ( P < 0.004) FI at 12 and 24 h in all animals after treatment. In response to NDP-MSH, 278 genes in hypothalamus ( q ≤ 0.07, P ≤ 0.001), 249 genes in liver ( q ≤ 0.07, P ≤ 0.001), and 5,066 genes in fat ( q ≤ 0.07, P ≤ 0.015) were differentially expressed. Pathway analysis of NDP-MSH-induced differentially expressed genes indicated that genes involved in cell communication, nucleotide metabolism, and signal transduction were prominently downregulated in the hypothalamus. In both liver and adipose tissue, energy-intensive biosynthetic and catabolic processes were downregulated in response to NDP-MSH. This included genes encoding for biosynthetic pathways such as steroid and lipid biosynthesis, fatty acid synthesis, and amino acid synthesis. Genes involved in direct energy-generating processes, such as oxidative phosphorylation, electron transport, and ATP synthesis, were upregulated, whereas TCA-associated genes were prominently downregulated in NDP-MSH-treated pigs. Our data also indicate a metabolic switch toward energy conservation since genes involved in energy-intensive biosynthetic and catabolic processes were downregulated in NDP-MSH-treated pigs.

scholarly journals Matrix metalloproteinase 14 (MMP14) is differentially expressed in breast cancer metastases.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Messenger Rna ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Primary Breast Tumor ◽  
Genomic Locus ◽  
Primary Tumors ◽  
Breast Cancer Metastases ◽  
Public Datasets

Breast cancer is a leading cause of death for women (1, 2). We mined public datasets to understand the most significant transcriptional and epigenomic changes between primary tumors of the breast and the metastases that they generate (3-6). In metastases to both the brain (3) and the bones (4), the matrix metalloproteinase 14 (MMP14) was among the genes whose expression changes most significantly between the transcriptomes of metastatic tissue to that of primary breast tumor. In metastases to the lymph nodes, a site at the MMP14 genomic locus contained significantly less methyl marks than the same site in primary tumors. The MMP14 gene was hypomethylated during spread of the breast cancer to the lymph node, MMP14 among the genes whose expression changed most significantly across the entire brain and bone transcriptome, and MMP14 messenger RNA was expressed at significantly lower levels in metastases across both tissues. Interestingly, primary tumors with metastatic potential expressed higher levels of MMP14 than primary tumors without metastatic potential. MMP14 is a target of interest in metastatic breast cancer.

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