scholarly journals Ellagic Acid Suppresses ApoB Secretion and Enhances ApoA-1 Secretion from Human Hepatoma Cells, HepG2

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3885
Author(s):  
Ayana Ieda ◽  
Maki Wada ◽  
Yuuki Moriyasu ◽  
Yuuko Okuno ◽  
Nobuhiro Zaima ◽  
...  

The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Ana Soto ◽  
Gracen Brilmyer

In the late 1980s, Professor of Immunology Ana Soto accidentally discovered the presence of synthetic estrogens in her lab equipment. Her lab had designed an experiment to test the effect of estrogen on the proliferation of human breast cancer cells (MCF7). Based on previous findings, Soto and her research partner Carlos Sonnenschein believed that, contrary to popular wisdom, the introduction of estrogen would not directly induce the proliferation of the cells, but would instead interfere with a naturally occurring inhibitor in the blood. But the control setup containing positive and negative controls (used in the past without problem) was now producing odd readings: although no estrogenic compound had been introduced, the cancer cells were still proliferating. Soto and Sonnenschein methodically removed each item in the control setup that might be producing the estrogen-like result. When they discovered that the estrogenic activity leached from the plastic centrifuge tubes used to store components of the cell culture medium, they called the manufacturer to find out what could have changed. The manufacturer let them know that the constituent materials of the tubes had recently been modified in order to reduce the possibility of breakage during centrifugation but declined to reveal what specific changes had been made. So Soto’s lab turned to studying the tubes themselves. After a year of further research, they concluded that the estrogenic activity was due to the additive that had been introduced by the manufacturer—nonylphenol, an antioxidant used in numerous other applications, some of which are meant for human use (e.g., spermicide) and the synthesis of detergents. Soto and Sonnenschein’s  assay is called E-SCREEN and  has been enormously influential; in fact, most of the environmental estrogens discovered in the 1990s rely on it. Conducted by Gracen Brilmyer at UCLA during the Chemical Entanglements Symposium, this 2017 interview with Soto highlights her experiences of sexism in the sciences and how those experiences have shaped her thinking on language, science, and scholarship


2021 ◽  
Vol 8 ◽  
Author(s):  
Yukina Kuwahara ◽  
Karin Yoshizaki ◽  
Hidetaka Nishida ◽  
Hiroaki Kamishina ◽  
Sadatoshi Maeda ◽  
...  

Mesenchymal stem/stromal cells (MSCs) have been used as cell sources for treating dogs with naturally-occurring diseases. Extracellular vesicles (EVs) derived from MSCs are now recognized as pivotal to modulating the immune response and supporting tissue repair. Manufacture of MSC-EVs for clinical application mandates removal of the xeno-proteins, including fetal bovine serum. The objective of this study was to examine whether canine MSCs survived and secreted EVs in serum-free medium (SFM) conditions and to assess the immunomodulatory effect of EVs in vitro. Canine MSCs were found to survive and secrete EVs under SFM conditions. The surface markers of MSCs in the SFM were similar to MSCs in complete culture medium. Canine MSC-EVs had a diameter of ~300 nm and were positive for EV markers. MSC-derived EVs from the serum-free condition reduced the levels of IL-1β by BV-2 cells in response to LPS stimulation. These results warrant further studies of the use of SFM for producing EVs derived from canine MSCs.


1977 ◽  
Author(s):  
J. H. Joist ◽  
J. F. Cowan ◽  
M. Khan

Rapid prolongation of the activated partial thromboplastin time (aPTT) of normal plasma upon incubation with ellagic acid containing aPTT reagents was observed. The aPTT prolongation was not due to time dependent changes in pH in the incubation mixtures or loss of activity of the labile coagulation factors VIII and V, but occurred as a result of rapid progressive inactivation of ellagic acid activated factors XII and XI. Prolongation of the aPTT and loss of contact factor activities was not observed in plasma incubated with particulate activator reagents. This finding seemed to indicate that adsorption of factors XII and XI to larger particles during the activation process may protect these factors from inactivation by naturally occurring plasma inhibitors. Evidence is presented which supports previous observations that Ci-inhibitor, α1-antitrypsin and antithrombin III (in the presence of heparin contribute to factor XIIa- and XIa-inactivation in ellagic acid activated plasma and that plasma albumin may compete with factor XII for ellagic acid binding. The findings indicate that ellagic acid containing aPTT reagents have unfavorable properties which seriously limit their usefulness in the clinical laboratory, particularly in respect to recording of the aPTT with certain fully automated clot timers.


1994 ◽  
Vol 345 (1313) ◽  
pp. 251-256 ◽  

Programmed death is a ubiquitous feature of the development of the vertebrate nervous system. This death is prevented in vivo by trophic factors and by afferent input. Death of neurons can also be prevented in culture models of programmed death by trophic factors and by chronic depolarization with elevated concentrations of K + in the culture medium. The latter effect is mediated by Ca 2+ influx through voltage-gated channels and may prevent death by mimicking survival-promoting effects of naturally occurring electrical activity. Little is currently known about the mechanism by which either trophic factors or increased cytoplasmic Ca 2+ promote survival.


HortScience ◽  
1990 ◽  
Vol 25 (9) ◽  
pp. 1078c-1078 ◽  
Author(s):  
S. Y. Wang ◽  
J. L. Maas ◽  
E. M. Daniel ◽  
G. J. Galletta

Ellagic acid (EA) a naturally occurring polyphenol in many fruit and nut crops, is a putative inhibitor of certain chemically-induced cancers. Improved methods of extraction, detection and quantification are essential for accurate determination of EA for plant physiological and genetic studies and animal nutrition and chemopreventative studies. Column (C18) preconditioning significantly reduced column retention of EA. An ammonium phosphate/methanol solvent system was used in preference to sodium phosphate/methanol. Fruit sample determinations were 10-100 times higher than previously reported, due to the improvements in efficiency of these methods. EA levels (mg/g dry wt) were: strawberry pulp (1.55), achene (8.46), root (1.55), crown (3.32) and leaf (14.27); blackberry pulp (,2.43) and seed (3.37); and cranberry skin (1.06), pulp (0.31), seed (0.69), leaf (4.10).


2019 ◽  
Vol 6 (14) ◽  
pp. 873-881
Author(s):  
Clayton dos Santos Silva ◽  
João Manoel da Silva ◽  
José Ubaldo Lima de Oliveira ◽  
Romário Guimarães Verçosa de Araújo ◽  
Jessé Rafael Bento de Lima ◽  
...  

The aim of this study was to isolate and select bacteria from the cacti rhizosphere naturally occurring in an adverse environment in culture medium under water stress. Samples of rhizospheric cacti soil were collected in two distinct locations with natural occurrence of the Caatinga vegetation of the Alagoas State, Northeast Brazil. With the use of culture-dependent methodologies, the isolation and purification of the bacteria was performed for exopolysaccharide production analyzes by quantification of halos and biofilm formation in a spectrophotometer under optical density (OD) of 560 nm. In total, 42 strains were isolated, with the isolates BCM02, BCM06, BCM10 and BCM13 being the major producers of EPS, followed by bacteria BCM01, BCM05, BCM28 and BCM35 with medium production, and bacteria BCM22 and BCM33 with low production. On the other hand, for the biofilm formation, all the isolates were efficient in the synthesis of the same, being 38% of the bacteria with high formation performance. Thus, strains BCM02 and BCM28 presented the best results in evaluations of water stress tolerance mechanisms, and could later be used for future tests to promote plant growth.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Liye Zhou ◽  
Mahmood Hussain

Objective: MicroRNAs (miRs) play important regulatory roles in lipid and lipoprotein metabolism. ApoB, as the only essential scaffolding protein in the assembly of very low density lipoproteins, is a target to treat hyperlipidemia and atherosclerosis. We aimed to find out miRs that reduce apoB expression. Approach: Bioinformatics analyses predicted that hsa-miR-548p can interact with apoB mRNA.MiR-548p mimic and control were transfected in human and mouse hepatoma cell lines to test its role in regulating apoB secretion and mRNA expression levels. Site-directed mutagenesis was used to identify the interacting site of miR-548p in human apoB 3′-untranslated region. Fatty acid oxidation and lipid syntheses were examined in miR-548p overexpressing cells to investigate its function in lipid metabolism. Results: Experimentally, we observed that miR-548p significantly reduces apoB secretion from human hepatoma cells in time and dose dependent manner. Mechanistic studies showed that miR-548p interacts with the 3′-untranslated region of human apoB mRNA to enhance posttranscriptional degradation. Bioinformatics algorithms suggested two potential binding sites of miR-548p on human apoB mRNA. Site-directed mutagenesis studies revealed that miR-548p targets site II involving both seed and supplementary sequences. MiR-548p had no effect on fatty acid oxidation but significantly decreased lipid synthesis in human hepatoma cells by reducing the expression of HMGCR and ACSL4 enzymes involved in cholesterol and fatty acid synthesis. In summary, miR-548p reduces lipoprotein production and lipid synthesis by reducing expression of different genes in human hepatoma cells. Conclusion: These studies suggest that miR-548p could be useful in treating atherosclerosis, hyperlipidemia and hepatosteatosis.


1986 ◽  
Vol 7 (10) ◽  
pp. 1663-1667 ◽  
Author(s):  
Robert C. Smart ◽  
Mou-Tuan Huang ◽  
Richard L. Chang ◽  
Jane M. Sayer ◽  
Donald M. Jerina ◽  
...  

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