scholarly journals Regulation of the gap junction connexin 43 gene by androgens in the prostate

2001 ◽  
Vol 26 (1) ◽  
pp. 1-10 ◽  
Author(s):  
HT Huynh ◽  
L Alpert ◽  
DW Laird ◽  
G Batist ◽  
L Chalifour ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Prostate Gland ◽  
Physiological Role ◽  
Prostate Tissue ◽  
Ventral Prostate ◽  
Gap Junctional Intercellular Communication ◽  
Prostate Carcinogenesis ◽  
Cx43 Mrna ◽  
And Function ◽  
Gap Junctional

Androgens play an important role in prostate gland development and function, and have been implicated in prostate carcinogenesis. We report the regulation of the gap junctional intercellular communication gene connexin 43 (Cx43) by androgens in the prostate gland. In rat ventral prostate tissue, only trace levels of Cx43 mRNA were detected. Castration, however, resulted in a high increase in Cx43 mRNA and protein. Cx32 was unchanged. Castration-induced Cx43 mRNA and protein were abolished by administration of dihydrotestosterone (DHT). Following castration, prostate weights were approximately 16% of sham-treated controls. However, DHT replacement resulted in prostate weights which were not different from sham-treated controls. Under similar castration conditions, Cx43 induction coincided with pronounced apoptosis in the prostate gland cells, and DHT prevented the induction of apoptosis. Given the physiological role of gap junctions and androgens in the regulation of prostate tissue homeostasis, our observations are relevant to the understanding of androgen-dependent prostate carcinogenesis.

miR-130b regulates gap junctional intercellular communication through connexin 43 in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Vol 26 (8) ◽  
pp. 576-584
Author(s):  
Linlin Jiang ◽  
Hui Huang ◽  
Yifan Qian ◽  
Yu Li ◽  
Xiaoli Chen ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Polycystic Ovary ◽  
Gap Junctional Intercellular Communication ◽  
Ovary Syndrome ◽  
Ovarian Cortex ◽  
Cx43 Mrna ◽  
Gap Junctional

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. We explored whether connexin 43 (Cx43) was differently expressed in luteinized granulosa cells from women with polycystic ovary syndrome (PCOS) compared with luteinized granulosa cells from women with a normal menstrual cycle, and whether certain miRNAs regulate the Cx43 level and gap junctional intercellular communication (GJIC). The miRNA profile was investigated in ovarian cortex tissues from five women with PCOS and five women without PCOS using a miRNA microarray. The levels of miR-130b and Cx43 mRNA were measured using real-time PCR in human luteinized granulosa cells from 20 women with PCOS and 25 women without PCOS. Protein and mRNA expression analysis and luciferase assays were conducted to confirm the substrate of miR-130b. PCOS ovarian cortex showed differential expression of miRNAs compared with non-PCOS ovarian cortex. Furthermore, miR-130b levels were increased in PCOS ovarian cortex and in luteinized granulosa cells compared with those in women with normal menstrual cycles, whereas the level of Cx43 mRNA, the identified target of miR-130b, was decreased in granulosa cells from patients with PCOS. Overexpression of miR-130b in a granulosa cell line resulted in reduced Cx43 protein levels and inhibited GJIC using scrape loading and dye transfer assay. Meanwhile, inhibition of miR-130b increased the Cx43 level. In conclusion, miR-130b was increased in PCOS granulosa cells, where it targets Cx43 to affect GJIC. The results of the present study suggested that miR-130b, via post-transcriptional regulation of Cx43, is involved in the pathophysiology of PCOS, which provides new insight into the pathological mechanism of PCOS.

scholarly journals Ouabain Modulates the Distribution of Connexin 43 in Epithelial Cells

2016 ◽  
Vol 39 (4) ◽  
pp. 1329-1338 ◽  
Author(s):  
Arturo Ponce ◽  
Isabel Larre ◽  
Aida Castillo ◽  
Catalina Flores-Maldonado ◽  
Odette Verdejo-Torres ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Connexin 43 ◽  
Mdck Cells ◽  
Physiological Role ◽  
Gap Junctional Intercellular Communication ◽  
Cell Contacts ◽  
Physiological Processes ◽  
Gap Junctional ◽  
Number Of Cells

Background/Aims: The fact that ouabain has been identified as an endogenous substance, led us to inquire its physiological role in epithelial cells. Based on previous observations, we hypothesized that it influences processes related to cell contacts. Previously we have shown that nanomolar concentrations of ouabain up-regulate tight junctions, accelerate ciliogenesis, and increase gap junctional intercellular communication (GJIC). Given that silencing assays indicated that connexin 43 (Cnx43) is involved in the GJIC response, in the present work we study whether ouabain affects Cnx43 expression and distribution. Methods: We seeded confluent monolayers of epithelial renal MDCK cells and incubated them with 10 nM ouabain during 1 h. Then we measured, by densitometric analysis of Western blot assays, the amount of Cnx43 in cells and in fractions enriched of plasma membrane. We also studied its localization with immunofluorescence and confocal microscopy. Results: Cnx43 is remarkably displayed, outlining the borders of cells gathered in clusters, randomly scattered throughout the monolayer. Ouabain increases the density of such clusters, as well as the average number of cells per cluster, without inducing the synthesis of new Cnx43. It also promotes relocation towards the membrane, of subunits already available. The fact that such changes are inhibited by PP2 and PD98059 indicates that a signaling pathway, that includes c-Src and ERK1/2, is involved in this response. Conclusion: Ouabain induces the translocation of Cnx43 from the cytoplasm to the plasma membrane. These findings support our hypothesis that one of the physiological roles of ouabain is the modulation of physiological processes that depend on cell to cell contacts.

Doxorubicin induces EGF receptor-dependent downregulation of gap junctional intercellular communication in rat liver epithelial cells

2005 ◽  
Vol 386 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Kotb Abdelmohsen ◽  
Claudia von Montfort ◽  
Dominik Stuhlmann ◽  
P. Arne Gerber ◽  
Ulrich K.M. Decking ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rat Liver ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Egf Receptor ◽  
Gap Junctional Intercellular Communication ◽  
Erk Activation ◽  
Liver Epithelial Cells ◽  
Rat Liver Epithelial Cells ◽  
Gap Junctional

Abstract Exposure of rat liver epithelial cells to doxorubicin, an anthraquinone derivative widely employed in cancer chemotherapy, led to a dose-dependent decrease in gap junctional intercellular communication (GJC). Gap junctions are clusters of inter-cellular channels consisting of connexins, the major connexin in the cells used being connexin-43 (Cx43). Doxorubicin-induced loss of GJC was mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK-2, as demonstrated using inhibitors of ERK activation. Furthermore, activation of the epidermal growth factor (EGF) receptor by doxorubicin was responsible for ERK activation and the subsequent attenuation of GJC. Inhibition of GJC, however, was not by direct phosphorylation of Cx43 by ERK-1/2, whereas menadione, a 1,4-naphthoquinone derivative that was previously demonstrated to activate the same EGF receptor-dependent pathway as doxorubicin, resulting in downregulation of GJC, caused strong phos-phorylation of Cx43 at serines 279 and 282. Thus, ERK-dependent downregulation of GJC upon exposure to quinones may occur both by direct phosphorylation of Cx43 and in a phosphorylation-independent manner.

scholarly journals Cancer-Associated Fibroblasts Accelerate Malignant Progression of Non-Small Cell Lung Cancer via Connexin 43-Formed Unidirectional Gap Junctional Intercellular Communication

2018 ◽  
Vol 51 (1) ◽  
pp. 315-336 ◽  
Author(s):  
Min Luo ◽  
Yanmei Luo ◽  
Naiquan Mao ◽  
Guolin Huang ◽  
Cuifang Teng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Small Cell ◽  
Migration And Invasion ◽  
Cancer Associated Fibroblasts ◽  
Gap Junctional Intercellular Communication ◽  
Small Cell Lung ◽  
Metabolic Coupling ◽  
Gap Junctional

Background/Aims: Gap junctions, which are assembled by connexins, can directly connect the cytoplasm of adjacent cells and enable gap junctional intercellular communication (GJIC) as well as metabolic coupling between neighboring cells. Here, we investigated the role of connexin 43 (Cx43) and its derived GJIC in the interplay between non-small cell lung cancer (NSCLC) cells and cancer-associated fibroblasts (CAFs). Methods: CAFs and NSCLC cells were co-cultured with direct contact and separated using flow cytometry. Glucose uptake, lactate production, and the expression and activity of PKM-2 and LDH-A in sorted CAFs were measured by a colorimetric assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Meanwhile, E-cadherin and N-cadherin expression and the migration and invasion of sorted NSCLC cells were detected by western blotting, wound width, and Transwell assays. Pyruvate, acetyl-CoA, and citric acid levels, ATP levels, and LDH-B and α-KG activity in sorted NSCLC cells were determined by a colorimetric or fluorometric assay and ELISA, respectively. Functional GJIC between cells and the subcellular location of connexins were detected by a “Parachute” assay and immunofluorescence. Levels of α-SMA, Cx43, and LDH-B in tissue from patients with NSCLC were determined by immunohistochemistry. Results: Cx43 accumulated in the plasma membrane, which favored the assembly of asymmetric unidirectional GJIC from CAFs to NSCLC cells. CAFs underwent increased aerobic glycolysis and promoted the epithelial-mesenchymal transition, migration, and invasion of NSCLC cells. In contrast, NSCLC cells experienced enhanced oxidative phosphorylation upon CAF stimulation, with an increase in ATP generation and thereby activation of the PI3K/Akt and MAPK/ERK pathways. Metabolic coupling between CAFs and NSCLC cells was under the strict control of Cx43-formed unidirectional GJIC. Patients with high tri-expression of α-SMA, Cx43, and LDH-B had the shortest overall survival and relapse-free survival compared with those with individual overexpression or high bi-expression. Conclusion: Cx43-formed unidirectional GJIC plays a critical role in mediating close metabolic cooperation between CAFs and NSCLC cells to support the malignant progression of NSCLC.

scholarly journals Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function

2020 ◽  
Vol 127 (2) ◽  
pp. 284-297 ◽  
Author(s):  
Jianlin Zhang ◽  
Kevin P. Vincent ◽  
Angela K. Peter ◽  
Matthew Klos ◽  
Hongqiang Cheng ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Optical Mapping ◽  
Physiological Role ◽  
Cardiac Conduction ◽  
Scaffolding Protein ◽  
Surface Ecg ◽  
Associated Proteins ◽  
And Function ◽  
Nodal Tissue ◽  
Intact Heart

Rationale: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. Objective: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. Methods and Results: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. Conclusions: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.

scholarly journals Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hyo-Jung Lee ◽  
Hyo-Jeong Lee ◽  
Eun Jung Sohn ◽  
Eun-Ok Lee ◽  
Jin-Hyoung Kim ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Critical Role ◽  
Combined Treatment ◽  
Connexin 26 ◽  
Hacat Cells ◽  
Gap Junctional Intercellular Communication ◽  
Hacat Keratinocyte ◽  
Gap Junctional

Though melatonin was known to regulate gap junctional intercellular communication (GJIC) in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2-) treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2) at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS) in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26) and connexin 43 (Cx43) at mRNA and protein levels, but not that of connexin 30 (Cx30) in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs) more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM) and vitamin C (10 μg/mL) significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

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