Novel modes of oestrogen receptor agonism and antagonism by hydroxylated and chlorinated biphenyls, revealed by conformation-specific peptide recognition patterns

Sumbayev, Vadim V.; Jensen, Jan K.; Hansen, J. Lundsgaard; Andreasen, Peter A.

doi:10.1016/j.mce.2008.02.004

Cited by 15 publications

(9 citation statements)

References 26 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, granzyme B displays highest catalytic activity at neutral pH. Therefore, in cells producing it, this enzyme is stored in acidic granules to prevent its activation (27,34). However, when T cells such as Tregs (regulatory T cells) and CD8-positive cytotoxic T cells are ready to release granzyme B (34), formation of the multiprotein barrier by galectin-9, VISTA and Tim-3 could potentially lead to its release (leakage) from the granules, thus resulting in its activation within the cells that produce it.…”

Section: Discussionmentioning

confidence: 99%

“…A Biacore amino coupling kit was employed to immobilize galectin-9 on the chip surface and VISTA (as a fusion protein with Fc) as well as Fc alone were flowed through in order to assess interactions using a Biacore T200 instrument. Data analysis was performed using Biacore T200 software and also using exponential decay (GraphPad Prism), taking into account both association and dissociation (27).…”

Section: Surface Plasmon Resonancementioning

confidence: 99%

See 1 more Smart Citation

Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

Acute myeloid leukemia (AML), a blood/bone marrow cancer, is a severe and often fatal malignancy. AML cells are capable of impairing the anti-cancer activities of cytotoxic lymphoid cells. This includes the inactivation of natural killer (NK) cells and killing of T lymphocytes. Here we report for the first time that V-domain Ig-containing suppressor of T cell activation (VISTA), a protein expressed by T cells, recognizes galectin-9 secreted by AML cells as a ligand. Importantly, we found that soluble VISTA released by AML cells enhances the effect of galectin-9, most likely by forming multiprotein complexes on the surface of T cells and possibly creating a molecular barrier. These events cause changes in the plasma membrane potential of T cells leading to activation of granzyme B inside cytotoxic T cells, resulting in apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Surface Plasmon Resonancementioning

confidence: 99%

Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Maruyama et al [ 32 , 33 ] have shown that the diphenylmethane skeleton can have a steroid role. Bisphenol A has estrogenic activity and bisphenol AF and HPTE have agonist activity for ERα with antagonist activity for ERβ ( Figure 4 ).…”

Section: Non-steroidal Ligandsmentioning

confidence: 99%

Estrogen Receptor Ligands: A Review (2013–2015)

Farzaneh

Zarghi

2016

Sci. Pharm.

View full text Add to dashboard Cite

Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high-affinity compounds, provided that some basic structural requirements are present.

show abstract

“…An interesting method to bypass this problem is to exploit the ability of ER to change conformation upon ligand binding. Indeed, αβ/I peptide, a specific peptide motif belonging to ER interacting proteins, was demonstrated to recognize the active conformation of wt-ERα LBD [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors

et al. 2017

View full text Add to dashboard Cite

Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive methods to detect EDCs, which are detrimental even at very low concentrations. In this work, we propose a label-free surface plasmon resonance (SPR) biosensor method to detect specific EDCs (17 β-estradiol (E2), ethinyl-estradiol, 4-nonylphenol, tamoxifen) through their binding to estrogen receptor alpha (ERα). We show that the use of rationally designed ERα (as bio-recognition element) in combination with conformation-sensitive peptides (as amplification agent, resulting in increased responses) enables the detection of low parts per billion (ppb) levels of E2. As a proof of concept, this bioassay was used to detect E2 in (spiked) real water samples from fish farms, rivers and the sea at low ppb levels after concentration by solid phase extraction. In addition, the present SPR assay that combines a conformation-sensitive peptide with an array of ERα mutants is very promising for the assessment of the risk of potential estrogenic activity for chemical substances.

show abstract

Novel modes of oestrogen receptor agonism and antagonism by hydroxylated and chlorinated biphenyls, revealed by conformation-specific peptide recognition patterns

Cited by 15 publications

References 26 publications

Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity

Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity

Estrogen Receptor Ligands: A Review (2013–2015)

Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors

Contact Info

Product

Resources

About