The Protective Effect of Functional Connexin43 Channels on a Human Epithelial Cell Line Exposed to Oxidative Stress

Abstract

Cx43-mediated protection of ARPE-19 cells from oxidative stress-induced death is dependent on functional Cx43 channels.

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

“…Some studies suggest a cell protective role whereas others propose a cell destructive role (21)(22)(23). Moreover, whether Cx43 hemichannels and/or gap junctions are important for H 2 O 2 -mediated cell death is still under debate.…”

“…However, the mechanism underlying this Cx43-mediated ROS resistance in astrocytes has not been investigated, although several lines of evidence indicate the involve-ment of Cx43 gap junctions or hemichannels in H 2 O 2 -mediated cell death in epithelial cells and osteocytes (20 -23). In addition, whether Cx43 plays a protective or detrimental role in response to ROS-induced oxidative stress is still under debate (21)(22)(23). In the present study, we employed two different systems, one using Cx43 Ϫ/Ϫ astrocytes and another with Cx43 channel blockers, to carefully examine the importance of Cx43 expression and channel activity in H 2 O 2 -induced astrocytic death.…”

Connexin-related signaling in cell death: to live or let die?

“…22 Contradictory to the paradigm that GJIC facilitates apoptosis are a number of investigations showing that GJs may impede the occurrence of cell death (Figure 2). [103][104][105][106][107][108][109][110][111][112][113][114][115][116] In line with this notion are a number of reports describing induction of apoptosis by chemical GJIC inhibitors 107,108,[117][118][119] as well as by Cx mimetic peptides, 120 which are peptides identical to a short Cx sequence that act as GJ blockers. 121 Healthy cells may indeed provide their dying neighbors with rescue signals 3 or cells in danger may dilute toxic substances toward healthy neighbors through GJs.…”

The effect of connexin43 on the level of vascular endothelial growth factor in human retinal pigment epithelial cells

“…Transfection of these retroviral vectors and an empty vector control into the 293 GPG packaging cell line was performed as previously described, as was the subsequent retroviral infection of ARPE-19 cells [12,19]. ShRNA knockdown of Cx43 in ARPE-19 cells was performed as previously described [8,12]. Briefly, ARPE-19 cells were stably infected with a retroviral vector expressing either shRNA targeting Cx43 or a non-target sequence as control (Vs).…”

“…Of the 21 members of the human Cx family, Cx43 was chosen for this study due to its wide expression across tissue types and its presence in RPE cells [11]. Further, we have previously demonstrated that expression of Cx43 in RPE cells is protective against oxidative stress-induced cell death [12]. Interestingly, oxidative stress is another factor implicated in early ARMD pathogenesis [13] and in stimulation of VEGF secretion from the RPE [14,15].…”