MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions

2019 ◽  
Vol 400 (6) ◽  
pp. 787-799 ◽  
Author(s):  
Joana Pereira-Vieira ◽  
João Azevedo-Silva ◽  
Ana Preto ◽  
Margarida Casal ◽  
Odília Queirós
Keyword(s):  
Short Chain Fatty Acids ◽  
Glucose Starvation ◽  
Tumor Aggressiveness ◽  
Ph Homeostasis ◽  
Sensitive Cell Line ◽  
Basal Expression ◽  
Colorectal Cancer Cells ◽  
Cd147 Expression ◽  
The One ◽  
Tumor Agent

Abstract Monocarboxylate transporters (MCTs) inhibition leads to disruption in glycolysis, induces cell death and decreases cell invasion, revealing the importance of MCT activity in intracellular pH homeostasis and tumor aggressiveness. 3-Bromopyruvate (3BP) is an anti-tumor agent, whose uptake occurs via MCTs. It was the aim of this work to unravel the importance of extracellular conditions on the regulation of MCTs and in 3BP activity. HCT-15 was found to be the most sensitive cell line, and also the one that presented the highest basal expression of both MCT1 and of its chaperone CD147. Glucose starvation and hypoxia induced an increased resistance to 3BP in HCT-15 cells, in contrast to what happens with an extracellular acidic pH, where no alterations in 3BP cytotoxicity was observed. However, no association with MCT1, MCT4 and CD147 expression was observed, except for glucose starvation, where a decrease in CD147 (but not of MCT1 and MCT4) was detected. These results show that 3BP cytotoxicity might include other factors beyond MCTs. Nevertheless, treatment with short-chain fatty acids (SCFAs) increased the expression of MCT4 and CD147 as well as the sensitivity of HCT-15 cells to 3BP. The overall results suggest that MCTs influence the 3BP effect, although they are not the only players in its mechanism of action.

scholarly journals Benefits of fecal microbiota transplantation: A comprehensive review

2020 ◽  
Vol 14 (10) ◽  
pp. 1074-1080
Author(s):  
Muluneh Ademe
Keyword(s):  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Action Current ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
The One ◽  
Host Metabolism

A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam­mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.

scholarly journals Metabolism Characteristics of Lactic Acid Bacteria and the Expanding Applications in Food Industry

2021 ◽  
Vol 9 ◽  
Author(s):  
Yaqi Wang ◽  
Jiangtao Wu ◽  
Mengxin Lv ◽  
Zhen Shao ◽  
Meluleki Hungwe ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Food Industry ◽  
Short Chain Fatty Acids ◽  
Fermented Food ◽  
The Body ◽  
Fermented Foods ◽  
Metabolic Characteristics ◽  
The One

Lactic acid bacteria are a kind of microorganisms that can ferment carbohydrates to produce lactic acid, and are currently widely used in the fermented food industry. In recent years, with the excellent role of lactic acid bacteria in the food industry and probiotic functions, their microbial metabolic characteristics have also attracted more attention. Lactic acid bacteria can decompose macromolecular substances in food, including degradation of indigestible polysaccharides and transformation of undesirable flavor substances. Meanwhile, they can also produce a variety of products including short-chain fatty acids, amines, bacteriocins, vitamins and exopolysaccharides during metabolism. Based on the above-mentioned metabolic characteristics, lactic acid bacteria have shown a variety of expanded applications in the food industry. On the one hand, they are used to improve the flavor of fermented foods, increase the nutrition of foods, reduce harmful substances, increase shelf life, and so on. On the other hand, they can be used as probiotics to promote health in the body. This article reviews and prospects the important metabolites in the expanded application of lactic acid bacteria from the perspective of bioengineering and biotechnology.

scholarly journals Cooperative Regulation of ADE3 Transcription by Gcn4p and Bas1p in Saccharomyces cerevisiae

2009 ◽  
Vol 8 (8) ◽  
pp. 1268-1277 ◽  
Author(s):  
Yoo Jin Joo ◽  
Jung-Ae Kim ◽  
Joung Hee Baek ◽  
Ki Moon Seong ◽  
Kyung-Duk Han ◽  
...  
Keyword(s):  
Amino Acids ◽  
Metabolic Pathways ◽  
Gene Deletion ◽  
Promoter Structure ◽  
Basal Expression ◽  
Direct Binding ◽  
Responsive Element ◽  
The One

ABSTRACT The one-carbon response regulon is essential for the biosynthesis of nucleic acids as well as several amino acids. The ADE3 gene is known to encode a crucial one-carbon regulon enzyme, tetrahydrofolate synthase, which is involved in the biosynthesis of purine and the amino acids methionine and glycine. Therefore, the mechanism through which ADE3 transcription is regulated appears to be critical for the cross-talk among these metabolic pathways. Even so, the direct involvement of ADE3 transcription through gene-specific transcription factors has not been shown clearly. In this study, the promoter structure of the ADE3 gene was investigated in detail, and a genuine Gcn4p responsive element (GCRE) was confirmed among three putative GCRE elements in vivo and in vitro. Through gene deletion studies of Gcn4p and Bas1p, it was established that both factors are involved in the transcriptional regulation of the ADE3 gene. Direct binding to this GCRE and the occupancy of the ADE3 promoter by these factors were also confirmed. Taking these results together, we concluded that Gcn4p is responsible for the basal and inducible expression of the ADE3 gene, while Bas1p is required for its basal expression.

scholarly journals Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2437 ◽  
Author(s):  
Ran Chen ◽  
Marja Jäättelä ◽  
Bin Liu
Keyword(s):  
Cancer Cells ◽  
Extracellular Space ◽  
Storage Capacity ◽  
Aerobic Glycolysis ◽  
Ph Homeostasis ◽  
Extracellular Acidification ◽  
Lactate Fermentation ◽  
The One ◽  
Intracellular Milieu ◽  
Insight Into

Cancer cells generate large quantities of cytoplasmic protons as byproducts of aberrantly activated aerobic glycolysis and lactate fermentation. To avoid potentially detrimental acidification of the intracellular milieu, cancer cells activate multiple acid-removal pathways that promote cytosolic alkalization and extracellular acidification. Accumulating evidence suggests that in addition to the well-characterized ion pumps and exchangers in the plasma membrane, cancer cell lysosomes are also reprogrammed for this purpose. On the one hand, the increased expression and activity of the vacuolar-type H+−ATPase (V-ATPase) on the lysosomal limiting membrane combined with the larger volume of the lysosomal compartment increases the lysosomal proton storage capacity substantially. On the other hand, enhanced lysosome exocytosis enables the efficient release of lysosomal protons to the extracellular space. Together, these two steps dynamically drive proton flow from the cytosol to extracellular space. In this perspective, we provide mechanistic insight into how lysosomes contribute to the rewiring of pH homeostasis in cancer cells.

scholarly journals Homeostatic Response of Mouse renin Gene Transcription in a Hypertensive Environment Is Mediated by a Novel 5′ Enhancer

2018 ◽  
Vol 38 (7) ◽  
Author(s):  
Aki Ushiki ◽  
Hitomi Matsuzaki ◽  
Akiyoshi Fukamizu ◽  
Keiji Tanimoto
Keyword(s):  
Blood Pressure ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Feedback Mechanism ◽  
Enhancer Activity ◽  
Basal Expression ◽  
The One

ABSTRACT The renin-angiotensin system plays an essential role in blood pressure homeostasis. Because renin activity is reflected as a blood pressure phenotype, its gene expression in the kidney is tightly regulated by a feedback mechanism; i.e., renin gene transcription is suppressed in a hypertensive state. To address the molecular mechanisms controlling hypertension-responsive mouse renin (m Ren ) gene regulation, we deleted either 5′ (17-kb) or 3′ (78-kb) regions of the endogenous m Ren gene and placed the animals in a hypertensive environment. While the m Ren gene bearing the 3′ deletion was appropriately downregulated, the one bearing the 5′ deletion lost this hypertension responsiveness. Because the 17-kb sequence exhibited enhancer activity in vivo and in vitro , we narrowed down the enhancer to a 2.3-kb core using luciferase assays in As4.1 cells. When this 2.3-kb sequence was removed from the endogenous m Ren gene in the mouse, its basal expression was dramatically reduced, and the hypertension responsiveness was significantly attenuated. Furthermore, we demonstrated that the angiotensin II signal played an important role in m Ren gene suppression. We propose that in a hypertensive environment, the activity of this novel enhancer is attenuated, and, as a consequence, m Ren gene transcription is suppressed to maintain blood pressure.

Note on Selection of Coordinate Systems for Geodynamics

1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen
Keyword(s):  
Sea Level ◽  
The Other ◽  
Coordinate Systems ◽  
Mean Sea Level ◽  
The Earth ◽  
The One ◽  
Static Systems ◽  
Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

Junction of the Epithelium and Lamina Propria of the Bovine Rumen Mucosa

1967 ◽  
Vol 25 ◽  
pp. 68-69
Author(s):  
Al W. Stinson
Keyword(s):  
Osmium Tetroxide ◽  
Squamous Epithelium ◽  
Short Chain Fatty Acids ◽  
Chloride Ions ◽  
Fermentation Products ◽  
Ruminant Species ◽  
Protective Shield ◽  
Stratified Squamous Epithelium ◽  
Lead Hydroxide ◽  
Acetic Acids

The stratified squamous epithelium which lines the ruminal compartment of the bovine stomach performs at least three important functions. (1) The upper keratinized layer forms a protective shield against the rough, fibrous, constantly moving ingesta. (2) It is an organ of absorption since a number of substances are absorbed directly through the epithelium. These include short chain fatty acids, potassium, sodium and chloride ions, water, and many others. (3) The cells of the deeper layers metabolize butyric acid and to a lesser extent propionic and acetic acids which are the fermentation products of rumen digestion. Because of the functional characteristics, this epithelium is important in the digestive process of ruminant species which convert large quantities of rough, fibrous feed into energy.Tissue used in this study was obtained by biopsy through a rumen fistula from clinically healthy, yearling holstein steers. The animals had been fed a typical diet of hay and grain and the ruminal papillae were fully developed. The tissue was immediately immersed in 1% osmium tetroxide buffered to a pH of 7.4 and fixed for 2 hrs. The tissue blocks were embedded in Vestapol-W, sectioned with a Porter-Blum microtome with glass knives and stained with lead hydroxide. The sections were studied with an RCA EMU 3F electron microscope.

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