Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif

Yeast as a model system for identification of metabolic targets of a 'glucosamine complex' used as a therapeutic agent of osteoarthritis

This manuscript describes the effect of a glucosamine complex and its different constituents on the metabolism of yeast cells. Indeed, the yeast model biosystem offers important advantages in the understanding of basic cellular and molecular processes. For example, the possibility to differentiate aerobic and anaerobic metabolism allows the measurement of glycolysis and mitochondria importance in the control of energetic metabolism and stress-responsive. Yeast growth and division can be controlled efficiently and effectively by adjusting environmental conditions that mimic some aspect of those experienced by chondrocytes in an osteoarthritic milieu, such as low oxygen and nutriment availabilities, high oxidative stress, etc. The glucosamine complex or some of its components (glucosamine sulphate, MSM, Ribes nigrum and silicon) enhanced cellular proliferation and CO2 production of yeast cells cultured under severe conditions. In addition, it allows a larger output of protons from the cells into the medium. Glucosamine complex supplementation also boosted cellular resistance to stresses such as heat shock, H2O2-induced peroxidation and ethanol. The beneficial effects of the complex were primarily due to R. nigrum and to glucosamine sulphate components. The protective effect of the glucosamine complex can be explained by an increase of cellular energy level through intensification of mitochondrial functionality and intracellular machinery (anaerobic glycolysis). An additional effect on protein kinase activation is not unlikely. © 2008 Elsevier Masson SAS. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Deletion of QDR genes in a bioethanol-producing yeast strain reduces propagation of contaminating lactic acid bacteria.

Bacterial contaminations in yeast fermentation tanks are a recurring problem for the bioethanol production industry. Lactic acid bacteria (LAB), particularly of the genus Lactobacillus, are the most common contaminants. Their proliferation can reduce fermentation efficiency or even impose premature shutdown for cleaning. We have previously reported that laboratory yeast strains naturally excrete amino acids via transporters of the Drug: H+ Antiporter-1 (DHA1) family. This excretion allows yeast to cross-feed LAB, which are most often unable to grow without an external amino acid supply. Whether industrial yeast strains used in bioethanol production likewise promote LAB proliferation through cross-feeding has not been investigated. In this study, we first show that the yeast strain Ethanol Red used in ethanol production supports growth of Lactobacillus fermentum in an amino-acid-free synthetic medium. This effect was markedly reduced upon homozygous deletion of the QDR3 gene encoding a DHA1-family amino acid exporter. We further show that cultivation of Ethanol Red in a nonsterile sugarcane-molasses-based medium is associated with an increase in lactic acid due to LAB growth. When Ethanol Red lacked the QDR1, QDR2, and QDR3 genes, this lactic acid production was not observed and ethanol production was not significantly reduced. Our results indicate that Ethanol Red cultivated in synthetic or molasses medium sustains LAB proliferation in a manner that depends on its ability to excrete amino acids via Qdr transporters. They further suggest that using mutant industrial yeast derivatives lacking DHA1-family amino acid exporters may be a way to reduce the risk of bacterial contaminations during fermentation.info:eu-repo/semantics/publishe

Deletion of QDR genes in a bioethanol-producing yeast strain reduces propagation of contaminating lactic acid bacteria

Abstract Bacterial contaminations in yeast fermentation tanks are a recurring problem for the bioethanol production industry. Lactic acid bacteria (LAB), particularly of the genus Lactobacillus, are the most common contaminants. Their proliferation can reduce fermentation efficiency or even impose premature shutdown for cleaning. We have previously reported that laboratory yeast strains naturally excrete amino acids via transporters of the Drug: H+ Antiporter-1 (DHA1) family. This excretion allows yeast to cross-feed LAB, which are most often unable to grow without an external amino acid supply. Whether industrial yeast strains used in bioethanol production likewise promote LAB proliferation through cross-feeding has not been investigated. In this study, we first show that the yeast strain Ethanol Red used in ethanol production supports growth of Lactobacillus fermentum in an amino-acid-free synthetic medium. This effect was markedly reduced upon homozygous deletion of the QDR3 gene encoding a DHA1-family amino acid exporter. We further show that cultivation of Ethanol Red in a nonsterile sugarcane-molasses-based medium is associated with an increase in lactic acid due to LAB growth. When Ethanol Red lacked the QDR1, QDR2, and QDR3 genes, this lactic acid production was not observed and ethanol production was not significantly reduced. Our results indicate that Ethanol Red cultivated in synthetic or molasses medium sustains LAB proliferation in a manner that depends on its ability to excrete amino acids via Qdr transporters. They further suggest that using mutant industrial yeast derivatives lacking DHA1-family amino acid exporters may be a way to reduce the risk of bacterial contaminations during fermentation