scholarly journals Mechanism for modulation of gating of connexin26-containing channels by taurine

2011 ◽  
Vol 138 (3) ◽  
pp. 321-339 ◽  
Author(s):  
Darren Locke ◽  
Fabien Kieken ◽  
Liang Tao ◽  
Paul L. Sorgen ◽  
Andrew L. Harris
Keyword(s):  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Taurine Transporter ◽  
Channel Modulation ◽  
Proximal Half ◽  
Sensitive Site ◽  
Interdomain Interaction ◽  
Ph Dependent ◽  
Carboxyl Terminal ◽  
Dependent Interaction

The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Gene Transcription as a Therapeutic Target in Leukemia

2021 ◽  
Vol 22 (14) ◽  
pp. 7340
Author(s):  
Alvina I. Khamidullina ◽  
Ekaterina A. Varlamova ◽  
Nour Alhuda Hammoud ◽  
Margarita A. Yastrebova ◽  
Alexandra V. Bruter
Keyword(s):  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Mechanisms Of Action ◽  
Special Program ◽  
Cell Plasticity ◽  
Hematopoietic Stem ◽  
Promising Strategy ◽  
Tumor Cell Plasticity ◽  
Transcriptional Landscape

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.

pH-dependent Interaction of Rhodopsin with Cyanidin-3-glucoside. 2. Functional Aspects

2009 ◽  
Vol 85 (2) ◽  
pp. 463-470 ◽  
Author(s):  
Kalyan C. Tirupula ◽  
Fernanda Balem ◽  
Naveena Yanamala ◽  
Judith Klein-Seetharaman
Keyword(s):  
Functional Aspects ◽  
Ph Dependent ◽  
Dependent Interaction

pH-Dependent Interaction and Resultant Structures of Silica Nanoparticles and Lysozyme Protein

Langmuir ◽  
2014 ◽  
Vol 30 (6) ◽  
pp. 1588-1598 ◽  
Author(s):  
Sugam Kumar ◽  
Vinod K. Aswal ◽  
P. Callow
Keyword(s):  
Silica Nanoparticles ◽  
Ph Dependent ◽  
Dependent Interaction

FK778: New Cellular and Molecular Mechanisms of Action

2006 ◽  
Vol 38 (3) ◽  
pp. 757-761 ◽  
Author(s):  
S. Schrepfer ◽  
T. Deuse ◽  
F. Koch-Nolte ◽  
C. Detter ◽  
H. Reichenspurner
Keyword(s):  
Molecular Mechanisms ◽  
Mechanisms Of Action

Molecular Mechanisms of Action of Bacterial Exotoxins

1996 ◽  
Vol 284 (2-3) ◽  
pp. 170-206 ◽  
Author(s):  
Joachim Balfanz ◽  
Peter Rautenberg ◽  
Uwe Ullmann
Keyword(s):  
Molecular Mechanisms ◽  
Mechanisms Of Action

Pharmacological mechanism of topiramate in the prophylaxis and treatment of migraine: a review

2018 ◽  
pp. 190-195
Author(s):  
Emanuela Paz Rosas ◽  
Raisa Ferreira Costa ◽  
Silvania Tavares Paz ◽  
Ana Paula Fernandes da Silva ◽  
Manuela Freitas Lyra de Freitas
Keyword(s):  
Cortical Spreading Depression ◽  
Molecular Mechanisms ◽  
Spreading Depression ◽  
Neuronal Excitability ◽  
Mechanisms Of Action ◽  
World Population ◽  
Gamma Aminobutyric Acid ◽  
Pharmacological Mechanism ◽  
Calcium Ion Channels ◽  
Voltage Dependent

Objective: This review sought to bring evidence of studies addressing the mechanisms of action of topiramate in the prevention and treatment of migraine. Background: Migraine is a neurovascular disorder that affects a large part of the world population. The use of prophylactics contributes to the decrease in the frequency and severity of this disease. Among the antiepileptic drugs, the topiramate, has proven to be the most effective for the treatment of migraine. Although the mechanism of action of this drug is still not well elucidated in the literature, there are several molecular mechanisms proposed. Methodology: A survey was carried out in the literature, from February to March 2018, in different databases, using the descriptors: topiramate, migraine and mechanisms of action. After a careful selection, 25 manuscripts were chosen for this review. Results: Evidence from a number of studies has indicated that the main mechanisms of action of topiramate are related to the modulation of voltage-dependent sodium and calcium ion channels, blockade of excitatory glutamate transmission and inhibition by gamma-aminobutyric acid receptors (GABA), AMPA/kainate and some isoenzymes of carbonic anhydrase. In addition, topiramate is involved in the suppression of cortical spreading depression, besides influencing trigeminovascular activity, and neuronal excitability. Conclusion: Thus, topiramate could be involved in the prevention of major events of the pathophysiology of migraine. Acting directly on cortical spreading depression (DAC), trigeminovascular signals and decreased central sensitization of migraine pain.

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