Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

Johansen, David; Cruciani, Véronique; Sundset, Rune; Ytrehus, Kirsti; Mikalsen, Svein‐Ole

doi:10.1159/000331719

Cited by 56 publications

(59 citation statements)

References 50 publications

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“…Moreover, they are triggered to open by some stimulation, such as inflammation, mechanical stress or ischemia (Batra et al, 2012;Johansen et al, 2011;Karpuk et al, 2011). In our study, however, we demonstrated for the first time that connexin-mediated hemichannels are responsible for glucose uptake in OPCs, implying a role for oligodendroglial connexin hemichannels under physiological conditions.…”

Section: Inhibition Of Hemichannel Activity Impacts Opc Proliferationmentioning

confidence: 48%

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Niu

et al. 2016

Journal of Cell Science

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Oligodendrocyte precursor cells (OPCs) undergo a series of energyconsuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca 2+ elevation in OPCs, indicating a Ca 2+ -dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energymetabolism-directed oligodendroglial-targeted therapies.

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Section: Inhibition Of Hemichannel Activity Impacts Opc Proliferationmentioning

confidence: 48%

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Niu

et al. 2016

Journal of Cell Science

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“…A naturally occurring cytoplasmic C-terminal fragment of Cx43, ~20 kDa in size, has been described and characterized in cultured murine and hamster cells and after Cx43 overexpression in human HeLa cells [7]. Others have also reported Cx43 immunoreactive bands of ~20 kDa, such as in glioma cells [8] and in neonatal rat heart myofibroblasts [9]. A 20-kDa Cx43 immunoreactive band is also clearly detected in zebrafish heart 48 hours postfertilization [10], and the authors also noted an ~30-kDa band in zebrafish ovaries.…”

Section: Resultsmentioning

confidence: 99%

Internal translation of the connexin 43 transcript

et al. 2014

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BackgroundConnexin 43 (Cx43), the most widely expressed gap junction protein, is associated with a number of physiological and pathological conditions. Many functions of Cx43 have been shown to be independent of gap junction formation and only require the expression of Cx43 C-terminal fragments. Recent evidence demonstrated that naturally occurring C-terminal isoforms can be generated via internal translation.FindingsHere, we confirm that C-terminal domains of Cx43, particularly the major 20-kDa isoform, can be independently generated and regulated by internal translation of the same single GJA1 gene transcript that encodes full-length Cx43. Through direct RNA transfection experiments, we provide evidence that internal translation is not due to a bona fide cap-independent IRES-mediated mechanism, as upstream ribosomal scanning or translation is required. In addition to the mTOR pathway, we show for the first time, using both inhibitors and cells from knockout mice, that the Mnk1/2 pathway regulates the translation of the main 20-kDa isoform.ConclusionsInternal translation of the Cx43 transcript occurs but is not cap-independent and requires translation upstream of the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20-kDa isoform is regulated by the Mnk1/2 pathway. Our results have major implications for past and future studies describing gap junction-independent functions of Cx43 in cancer and other pathological conditions. This study provides further clues to the signalling pathways that regulate internal mRNA translation, an emerging mechanism that allows for increased protein diversity and functional complexity from a single mRNA transcript.

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“…This study confirms that blockade of connexin hemichannel opening by Gap26 confers protection to intact heart against ischemia-reperfusion injury regardless of the administration before or after the occurrence of ischemia (Hawat et al, 2010). Another study also shows that opening of Cx43 hemichannels during ischemia-reperfusion appears to be an important mechanism for ischemia-reperfusion injury in the heart given that Gap26 significantly reduces the infarct/risk ratio (Johansen et al, 2011). However, the alternative hemichannel, pannexin channel is not involved.…”

Section: Connexin Hemichannelsmentioning

confidence: 99%

Connexin channel and its role in diabetic retinopathy

Roy

Jiang

et al. 2017

Progress in Retinal and Eye Research

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Diabetic retinopathy is the leading cause of blindness in the working age population. Unfortunately, there is no cure for this devastating ocular complication. The early stage of diabetic retinopathy is characterized by the loss of various cell types in the retina, namely endothelial cells and pericytes. As the disease progresses, vascular leakage, a clinical hallmark of diabetic retinopathy, becomes evident and may eventually lead to diabetic macular edema, the most common cause of vision loss in diabetic retinopathy. Substantial evidence indicates that the disruption of connexin-mediated cellular communication plays a critical role in the pathogenesis of diabetic retinopathy. Yet, it is unclear how altered communication via connexin channel mediated cell-to-cell and cell-to-extracellular microenvironment is linked to the development of diabetic retinopathy. Recent observations suggest the possibility that connexin hemichannels may play a role in the pathogenesis of diabetic retinopathy by allowing communication between cells and the microenvironment. Interestingly, recent studies suggest that connexin channels may be involved in regulating retinal vascular permeability. These cellular events are coordinated at least in part via connexin-mediated intercellular communication and the maintenance of retinal vascular homeostasis. This review highlights the effect of high glucose and diabetic condition on connexin channels and their impact on the development of diabetic retinopathy.

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Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

Cited by 56 publications

References 50 publications

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Internal translation of the connexin 43 transcript

Connexin channel and its role in diabetic retinopathy

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