scholarly journals Low pH enhances connexin32 degradation in the pancreatic acinar cell

2014 ◽  
Vol 307 (1) ◽  
pp. G24-G32 ◽  
Author(s):  
Anamika M. Reed ◽  
Thomas Kolodecik ◽  
Sohail Z. Husain ◽  
Fred S. Gorelick
Keyword(s):  
Gap Junctions ◽  
Acinar Cell ◽  
Intercellular Communication ◽  
Pancreatic Acinar Cell ◽  
Low Ph ◽  
Extracellular Ph ◽  
Gap Junctional Intercellular Communication ◽  
Junction Protein ◽  
Clinical Conditions ◽  
Gap Junctional

Decreased extracellular pH is observed in a number of clinical conditions and can sensitize to the development and worsen the severity of acute pancreatitis. Because intercellular communication through gap junctions is pH-sensitive and modulates pancreatitis responses, we evaluated the effects of low pH on gap junctions in the rat pancreatic acinar cell. Decreasing extracellular pH from 7.4 to 7.0 significantly inhibited gap junctional intracellular communication. Acidic pH also significantly reduced levels of connexin32, the predominant gap junction protein in acinar cells, and altered its localization. Increased degradation through the proteasomal, lysosomal, and autophagic pathways mediated the decrease in connexin32 under low-pH conditions. These findings provide the first evidence that low extracellular pH can regulate gap junctional intercellular communication by enhancing connexin degradation.

scholarly journals High-throughput measurement of gap junctional intercellular communication

2014 ◽  
Vol 306 (12) ◽  
pp. H1708-H1713 ◽  
Author(s):  
Jun Liu ◽  
Vinayakumar Siragam ◽  
Jun Chen ◽  
Michael D. Fridman ◽  
Robert M. Hamilton ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Cell Lines ◽  
High Throughput ◽  
Intercellular Communication ◽  
Dye Transfer ◽  
Gap Junctional Intercellular Communication ◽  
Cell Injection ◽  
Operation Speed ◽  
Gap Junctional

Gap junctional intercellular communication (GJIC) is a critical part of cellular activities and is necessary for electrical propagation among contacting cells. Disorders of gap junctions are a major cause for cardiac arrhythmias. Dye transfer through microinjection is a conventional technique for measuring GJIC. To overcome the limitations of manual microinjection and perform high-throughput GJIC measurement, here we present a new robotic microinjection system that is capable of injecting a large number of cells at a high speed. The highly automated system enables large-scale cell injection (thousands of cells vs. a few cells) without major operator training. GJIC of three cell lines of differing gap junction density, i.e., HeLa, HEK293, and HL-1, was evaluated. The effect of a GJIC inhibitor (18-α-glycyrrhetinic acid) was also quantified in the three cell lines. System operation speed, success rate, and cell viability rate were quantitatively evaluated based on robotic microinjection of over 4,000 cells. Injection speed was 22.7 cells per min, with 95% success for cell injection and >90% survival. Dye transfer cell counts and dye transfer distance correlated with the expected connexin expression of each cell type, and inhibition of dye transfer correlated with the concentration of GJIC inhibitor. Additionally, real-time monitoring of dye transfer enables the calculation of coefficients of molecular diffusion through gap junctions. This robotic microinjection dye transfer technique permits rapid assessment of gap junction function in confluent cell cultures.

Loss of gap junctional intercellular communication in rat lung epithelial cells exposed to carbon or silica-based nanoparticles

2010 ◽  
Vol 391 (11) ◽  
Author(s):  
Niloofar Ale-Agha ◽  
Catrin Albrecht ◽  
Lars-Oliver Klotz
Keyword(s):  
Epithelial Cells ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Lung Epithelial Cells ◽  
Rat Lung ◽  
Dye Transfer ◽  
Gap Junctional Intercellular Communication ◽  
Junction Protein ◽  
Lung Epithelial ◽  
Gap Junctional

Abstract The aim of this study was to investigate whether fine and ultrafine carbon black (fC and ufC), and fine and ultrafine silica (fS, ufS) particles affect gap junctional intercellular communication (GJIC) in rat lung epithelial cells. Exposure of cells to subcytotoxic doses of ufC, fS and ufS resulted in a 63%, 59% and 77% reduction of GJIC, respectively, as determined in a dye transfer assay. In contrast to ufC, fC did not significantly alter GJIC. Changes in subcellular localization of the major gap junction protein in RLE cells, connexin-43 (Cx43), and of β-catenin were observed in cells exposed to ufC, fS or ufS. The loss of GJIC was counteracted by N-acetyl cysteine and was largely prevented by specific inhibitors of epidermal growth factor receptor-dependent signaling, pointing to the crucial role of two known major mediators of nanoparticle action, namely reactive oxygen species and membrane-receptor signaling, in particle-induced modulation of GJIC.

Connexin mimetic peptides: specific inhibitors of gap-junctional intercellular communication

2001 ◽  
Vol 29 (4) ◽  
pp. 606-612 ◽  
Author(s):  
W. H. Evans ◽  
S. Boitano
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Gap Junctional Intercellular Communication ◽  
Reversible Inhibitors ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Wide Range ◽  
Mimetic Peptides ◽  
Gap Junctional ◽  
Specific Sequences

Intercellular co-operation is a fundamental and widespread feature in tissues and organs. An important mechanism ensuring multicellular homoeostasis involves signalling between cells via gap junctions that directly connect the cytosolic contents of adjacent cells. Cell proliferation and intercellular communication across gap junctions are closely linked, and a number of pathologies in which communication is disrupted are known where connexins, the gap-junctional proteins, are modified. The proteins of gap junctions thus emerge as therapeutic targets inviting the development and exploitation of chemical tools and drugs that specifically influence intercellular communication. Connexin mimetic peptides that correspond to short specific sequences in the two extracellular loops of connexins are a class of benign, specific and reversible inhibitors of gap-junctional communication that have been studied recently in a broad range of cells, tissues and organs. This review summarizes the properties and uses of these short synthetic peptides, and compares their probable mechanism of action with those of a wide range of other less specific traditional gap-junction inhibitors.

Modification of gap junctional intercellular communication by changes in extracellular pH in Syrian hamster embryo cells

1990 ◽  
Vol 11 (6) ◽  
pp. 909-913 ◽  
Author(s):  
Randall J. Ruch ◽  
James E. Klaunig ◽  
James E. Klaunig ◽  
Gary A. Kerckaert ◽  
Robert A. LeBoeuf ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Syrian Hamster ◽  
Extracellular Ph ◽  
Gap Junctional Intercellular Communication ◽  
Hamster Embryo Cells ◽  
Embryo Cells ◽  
Gap Junctional

scholarly journals Seeing Is Believing: Gap Junctions in Motion

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 494
Author(s):  
Xinbo Li
Keyword(s):  
Gap Junctions ◽  
Intercellular Communication ◽  
Plasma Membranes ◽  
Gap Junctional Intercellular Communication ◽  
Connexin Proteins ◽  
Gap Junctional

Gap junctional intercellular communication (GJIC) channels between cells are composed of connexin proteins that form hexamers (connexons) in adjacent plasma membranes [...]

scholarly journals Connexins and Gap Junctions in Cancer of the Urinary Tract

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 704 ◽  
Author(s):  
Thomas Tschernig
Keyword(s):  
Bladder Cancer ◽  
Urinary Tract ◽  
Gap Junctions ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Urinary Bladder Cancer ◽  
Gap Junctional Intercellular Communication ◽  
History Of ◽  
Gap Junctional

This review focuses on connexins and nexus or gap junctions in the genesis, progression, and therapy of carcinomas of the human urinary tract. Some decades ago, the idea was born that gap junctional intercellular communication might prevent both the onset and the progression of cancer. Later evidence indicated that, on the contrary, synthesis and the presence of connexins as a prerequisite for gap junctional intercellular communication might promote the occurrence of cancer and metastases. The research history of urinary bladder cancer is a good example of the development of scientific perception. So far, the role of gap junctional intercellular communication in carcinogenesis and cancer progression, as well as in therapeutical approaches, remains unclear.

Effects of cadmium on gap junctional intercellular communication in WB-F344 rat liver epithelial cells

2001 ◽  
Vol 20 (11) ◽  
pp. 577-583 ◽  
Author(s):  
S-H Jeong ◽  
M-H Cho ◽  
J-H Cho
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Gap Junctions ◽  
Cell Viability ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Tumor Promotion ◽  
Gap Junctional Intercellular Communication ◽  
Rat Liver Epithelial Cells ◽  
Gap Junctional

Cadmium has been associated with a number of tumors but its role in tumor promotion has not been elucidated clearly or the results obtained from various studies have been conflicting. This study was designed to investigate the effects of cadmium on the gap junctional intercellular communication (GJIC), number of gap junctions per cell, and cell proliferation in WB-F344 rat liver epithelial cells from the viewpoint of tumor promotion. GJIC was monitored by counting the cells stained with Lucifer yellow CH dye, using the scrape-loading and dye-transfer method. The numbers of gap junctions per cell were visually quantitated after an indirect immunostaining for gap junction protein using an antibody to connexin 43. Cell proliferation was assayed by direct counting of the living cells using the trypan blue dye exclusion method. In the time course study, cells treated with 200 μM CdCl2 showed rapid and nearly complete inhibition of GJIC (approximately 14% of the control) and a decrease in the number of gap junctions per cell (approximately 21% of the control) at 30 min, and the decrease continued up to 4 h without any changes in the cell viability. Treatment with CdCl2 7.4-200 μM) for 4 h resulted in the decrease of GJIC and gap junction numbers per cell in a dose-response pattern without changes in the cell viability. In the long-term (14 days) exposure studies at doses of 0.01-7.4 μM CdCl2, an increase in cell proliferation was observed at low doses of 0.03-2.5 μM CdCl2, with GJIC also decreasing. These data demonstrate that cadmium inhibits GJIC, reduces the number of gap junctions per cell, and induces cell proliferation while decreasing the function of the gap junction.

scholarly journals The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amos Fumagalli ◽  
Joyce Heuninck ◽  
Anne Pizzoccaro ◽  
Enora Moutin ◽  
Joyce Koenen ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Chemokine Receptor ◽  
Intercellular Communication ◽  
Intracellular Signaling ◽  
Connexin 43 ◽  
Gap Junctional Intercellular Communication ◽  
Functional Link ◽  
Embryonic Mouse ◽  
Junction Protein ◽  
Gap Junctional

Abstract The atypical chemokine receptor 3 (ACKR3) plays a pivotal role in directing the migration of various cellular populations and its over-expression in tumors promotes cell proliferation and invasiveness. The intracellular signaling pathways transducing ACKR3-dependent effects remain poorly characterized, an issue we addressed by identifying the interactome of ACKR3. Here, we report that recombinant ACKR3 expressed in HEK293T cells recruits the gap junction protein Connexin 43 (Cx43). Cx43 and ACKR3 are co-expressed in mouse brain astrocytes and human glioblastoma cells and form a complex in embryonic mouse brain. Functional in vitro studies show enhanced ACKR3 interaction with Cx43 upon ACKR3 agonist stimulation. Furthermore, ACKR3 activation promotes β-arrestin2- and dynamin-dependent Cx43 internalization to inhibit gap junctional intercellular communication in primary astrocytes. These results demonstrate a functional link between ACKR3 and gap junctions that might be of pathophysiological relevance.

Sign in / Sign up

Export Citation Format

Share Document