scholarly journals Connexin43 and AMPK Have Essential Role in Resistance to Oxidative Stress Induced Necrosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Chunshan Zhao ◽  
Jinnv Fang ◽  
Chunguo Li ◽  
Min Zhang
Keyword(s):  
Oxidative Stress ◽  
Cell Damage ◽  
Ros Production ◽  
Cx43 Expression ◽  
Ampk Signaling ◽  
Junction Protein ◽  
A Cell ◽  
Intercellular Channels ◽  
Gap Junction Protein

Reactive oxygen species (ROS) induced oxidative stress leads to cell damage and neurological disorders in astrocytes. The gap junction protein connexin43 (Cx43) could form intercellular channels in astrocytes and the expression of Cx43 plays an important role in protecting the cells from damage. In the present study, we investigated the contribution of Cx43 to astrocytic necrosis induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which AMPK was involved in this process. Fluorescence microscopy, flow cytometry, and western blot were used quantitatively and qualitatively to determine the cell apoptosis, necrosis, and protein expression. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased H2O2-induced astrocytic necrosis, supporting a cell protective effect of functional Cx43 channels. Our data suggest that AMPK is important for Cx43-mediated ROS resistance. Inhibition of AMPK activation results in reduction of necrosis and ROS production. Taken together, our findings suggest that the role of Cx43 in response to H2O2stress is dependent on the activation of AMPK signaling pathways and regulates ROS production and cell necrosis.

scholarly journals Gap Junction Intercellular Communication Mediated by Connexin43 in Astrocytes Is Essential for Their Resistance to Oxidative Stress

2013 ◽  
Vol 289 (3) ◽  
pp. 1345-1354 ◽  
Author(s):  
Hoa T. Le ◽  
Wun Chey Sin ◽  
Shannon Lozinsky ◽  
John Bechberger ◽  
José Luis Vega ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Cx43 Expression ◽  
Knock Out ◽  
Gap Junction Intercellular Communication ◽  
Junction Protein ◽  
A Cell ◽  
Hypoxia Reoxygenation

Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

scholarly journals How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights

2021 ◽  
Vol 22 (5) ◽  
pp. 2471
Author(s):  
Viviana Costa ◽  
Marcello De Fine ◽  
Valeria Carina ◽  
Alice Conigliaro ◽  
Lavinia Raimondi ◽  
...  
Keyword(s):  
Joint Inflammation ◽  
Loss Of Function ◽  
Cx43 Expression ◽  
Cell Functions ◽  
Genes Expression ◽  
Junction Protein ◽  
Kellgren And Lawrence ◽  
Gap Junction Protein ◽  
The Common

Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.

MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

2020 ◽  
Vol 21 (12) ◽  
pp. 1216-1224
Author(s):  
Fatemeh Forouzanfar ◽  
Samira Asgharzade
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Cell Damage ◽  
Sensory Cells ◽  
Noise Induced Hearing Loss ◽  
Irreversible Damage ◽  
Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

scholarly journals Role of Gap Junction Protein Connexin43 in Astrogliosis Induced by Brain Injury

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47311 ◽  
Author(s):  
Nicolas Theodoric ◽  
John F. Bechberger ◽  
Christian C. Naus ◽  
Wun-Chey Sin
Keyword(s):  
Brain Injury ◽  
Gap Junction ◽  
Junction Protein ◽  
Gap Junction Protein

scholarly journals Involvement of the Gap Junction Protein, Connexin43, in the Formation and Function of Invadopodia in the Human U251 Glioblastoma Cell Line

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 117 ◽  
Author(s):  
Amandine Chepied ◽  
Zeinaba Daoud-Omar ◽  
Annie-Claire Meunier-Balandre ◽  
Dale W. Laird ◽  
Marc Mesnil ◽  
...  
Keyword(s):  
Gap Junction ◽  
Molecular Mechanisms ◽  
Glioblastoma Cells ◽  
Dynamic Interactions ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Gap Junction Protein ◽  
And Function ◽  
Low Cell Density ◽  
Invadopodia Formation

The resistance of glioblastomas to treatments is mainly the consequence of their invasive capacities. Therefore, in order to better treat these tumors, it is important to understand the molecular mechanisms which are responsible for this behavior. Previous work suggested that gap junction proteins, the connexins, facilitate the aggressive nature of glioma cells. Here, we show that one of them—connexin43 (Cx43)—is implicated in the formation and function of invadopodia responsible for invasion capacity of U251 human glioblastoma cells. Immunofluorescent approaches—combined with confocal analyses—revealed that Cx43 was detected in all the formation stages of invadopodia exhibiting proteolytic activity. Clearly, Cx43 appeared to be localized in invadopodia at low cell density and less associated with the establishment of gap junctions. Accordingly, lower extracellular matrix degradation correlated with less mature invadopodia and MMP2 activity when Cx43 expression was decreased by shRNA strategies. Moreover, the kinetics of invadopodia formation could be dependent on Cx43 dynamic interactions with partners including Src and cortactin. Interestingly, it also appeared that invadopodia formation and MMP2 activity are dependent on Cx43 hemichannel activity. In conclusion, these results reveal that Cx43 might be involved in the formation and function of the invadopodia of U251 glioblastoma cells.

Functional analysis of gap junctions in ovarian granulosa cells: distinct role for connexin43 in early stages of folliculogenesis

2003 ◽  
Vol 284 (4) ◽  
pp. C880-C887 ◽  
Author(s):  
Joanne E. I. Gittens ◽  
Abdul Amir Mhawi ◽  
Darcy Lidington ◽  
Yves Ouellette ◽  
Gerald M. Kidder
Keyword(s):  
Gap Junctions ◽  
Granulosa Cells ◽  
Significant Contribution ◽  
Ionic Current ◽  
Wild Type ◽  
Intercellular Coupling ◽  
Ovarian Granulosa Cells ◽  
Junction Protein ◽  
Gap Junction Protein

Ovarian granulosa cells are coupled via gap junctions containing connexin43 (Cx43 or α-1 connexin). In the absence of Cx43, granulosa cells stop growing in an early preantral stage. However, the fact that granulosa cells of mature follicles express multiple connexins complicated interpretation of this finding. The present experiments were designed to clarify the role of Cx43 vs. these other connexins in the earliest stages of folliculogenesis. Dye injection experiments revealed that granulosa cells from Cx43 knockout follicles are not coupled, and this was confirmed by ionic current injections. Furthermore, electron microscopy revealed that gap junctions are extremely rare in mutant granulosa cells. In contrast, mutant granulosa cells were able to form gap junctions with wild-type granulosa cells in a dye preloading assay. It was concluded that mutant granulosa cells contain a population of connexons, composed of an unidentified connexin, that do not normally contribute to gap junctions. Therefore, although Cx43 is not the only gap junction protein present in granulosa cells of early preantral follicles, it is the only one that makes a significant contribution to intercellular coupling.

scholarly journals Immunomodulatory role of phagocyte-derived chloramines involving lymphocyte glutathione

1993 ◽  
Vol 2 (3) ◽  
pp. 235-241 ◽  
Author(s):  
Véronique Witko-Sarsat ◽  
Anh Thu Nguyen ◽  
Béatrice Descamps-Latscha
Keyword(s):  
Oxidative Stress ◽  
Reduced Glutathione ◽  
Human Lymphocytes ◽  
Cell System ◽  
Polymorphonuclear Neutrophils ◽  
Myristate Acetate ◽  
Defensive Role ◽  
Free Model ◽  
A Cell

This study shows that human lymphocytes markedly decrease chloramines (long-lived oxidants) generated by polymorphonuclear neutrophils (PMN) after stimulation by phorbol-myristate-acetate or opsonized zymosan. In a cell-free model, reduced glutathione (GSH) scavenged chloramines, giving rise to oxidized glutathione (GSSG). In the cell system, treatment of lymphocytes with autologous PMN-derived chloramines induced a profound decrease in their total and reduced glutathione (GSH) content and markedly inhibited their proliferate responses to concanavalin-A and, to a lesser extent, phytohaemagglutinin. It is concluded that (i) lymphocytes may play a defensive role against phagocyte-derived oxidative stress by scavenging chloramines, and (ii) as this effect which is mediated by GSH affects lymphocyte proliferative responses, it may help to elucidate the still obscure mechanisms of oxidative stress associated immunodeficiency.

scholarly journals Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Cell Damage ◽  
Treated Group ◽  
Protective Role ◽  
Control Group ◽  
Similar Dose ◽  
Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

Freezing of Cells: Role of Ice and Solutes in Cell Damage

2007 ◽  
Author(s):  
Hiroshi Takamatsu
Keyword(s):  
Mechanical Stress ◽  
Cell Damage ◽  
Cellular Damage ◽  
Elevated Concentration ◽  
Cellular Injury ◽  
Extracellular Solution ◽  
Different Types ◽  
A Cell ◽  
The Difference

The mechanism of cellular damage associated with freezing of biological cells is discussed by summarizing the author’s recent studies that consists of four different types of experiments. The “solution effects” that designate the influence of elevated concentration of electrolytes during freezing is examined first by a nonfreezing experiment that exposes cells to hypertonic solutions using a perfusion microscope. The cell damage due to the solution effect is evaluated directly from a pseudo-freezing experiment, where cells were subjected to the milieu that simulated a freeze-thaw process in the absence of ice. Contribution of ice formed in the extracellular solution is then estimated from the difference in cell survival between the pseudo-freezing experiment and a corresponding freezing experiment. The cellular injury by the mechanical stress is also examined independently by a cell deformation experiment, which mimicked the situation that cells are compressed and deformed between ice crystals. This experiment was designed to examine a complex effect of mechanical stress from ice and elevated concentration of electrolytes. Based on all these experiments, the role of concentrated solutes and ice is revealed as a function of freezing conditions.

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