Connexin Channels, Connexin Mimetic Peptides and ATP Release

Leybaert, Luc; Braet, Katleen; Vandamme, Wouter; Cabooter, Liesbet; Martín, Patricia; Evans, William Howard

doi:10.1080/714040436

Cited by 38 publications

(53 citation statements)

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“…Here, we showed for the first time that superfusion of the ion channel-deficient tsA201 cells, transiently expressing Cx43, with Gap26 readily inhibits Cx43Hc-mediated currents recorded from individual cells. This observation complements with previous studies reporting on the inhibitory effect of Gap26 on the permeability of Cx43Hc [6,19,31,40], the second major functional characteristic of connexin channels besides conductance. Although not surprisingly, this result represents the most direct evidence reported so far for the Gap26 inhibitory effect on Cx43Hc.…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, synthetic connexin-deriving structural mimetic peptides (CxMPs) emerged as powerful and unique tools capable of blocking unapposed hemichannels with little or no immediate effects on GJC. While initially developed with the intention to modulate the function of GJC [7,8,16,17,30], subsequent studies unravelled their preferential action on unapposed hemichannels [5,6,18,19,31]. By mimicking short amino acid sequences on connexins extracellular loops, CxMPs bind to these structures and cause inhibition of unapposed hemichannels by a yet undetermined mechanism (see review by Dahl [15]).…”

Section: Introductionmentioning

confidence: 97%

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Connexin 43 mimetic peptide Gap26 confers protection to intact heart against myocardial ischemia injury

Hawat

Benderdour

Rousseau

et al. 2010

Pflugers Arch - Eur J Physiol

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Unapposed connexin 43 hemichannels (Cx43Hc) are present on sarcolemma of cardiomyocytes. Whereas Cx43Hc remain closed during physiological conditions, their opening under ischemic stress contributes to irreversible tissue injury and cell death. To date, conventional blockers of connexin channels act unselectively on both gap junction channels and unapposed hemichannels. Here, we test the hypothesis that Gap26, a synthetic structural mimetic peptide deriving from the first extracellular loop of Cx43 and a presumed selective blocker of Cx43Hc, confers resistance to intact rat heart against ischemia injury. Langendorff-perfused intact rat hearts were utilized. Regional ischemia was induced by 40-min occlusion of the left anterior descendent coronary and followed by 180 min of reperfusion. Gap26 was applied either 10 min before or 30 min after the initiation of ischemia. Interestingly, myocardial infarct size was reduced by 48% and 55% in hearts treated with Gap26 before or during ischemia, respectively, compared to untreated hearts. Additionally, myocardial perfusate flow was increased in both groups during reperfusion by 37% and 32%, respectively. Application of Gap26 increased survival of isolated cardiomyocytes after simulated ischemia-reperfusion by nearly twofold compared to untreated cells. On the other hand, superfusion of tsA201 cells transiently expressing Cx43 with Gap26 caused 61% inhibition of Cx43Hc-mediated currents recorded using the patch clamp technique. In summary, we demonstrate for the first time that Cx43 mimetic peptide Gap26 confers protection to intact heart against ischemia-reperfusion injury whether administered before or after the occurrence of ischemia. In addition, we provide unequivocal evidence for the inhibitory effect of Gap26 on genuine Cx43Hc.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 97%

Connexin 43 mimetic peptide Gap26 confers protection to intact heart against myocardial ischemia injury

Hawat

Benderdour

Rousseau

et al. 2010

Pflugers Arch - Eur J Physiol

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“…Nevertheless, the question remains if Cx43 could support oogenesis by forming undocked connexons in the granulosa cell plasma membranes. Those Cx43-based hemichannels could transfer ATP [128] to interact with receptors on adjacent cells, thereby establishing a paracrine signaling route to enhance calcium signals in oocytes [129,130]. The hypothesis that in granulosa cells the function of Cx43-based hemichannels might be more important for folliculogenesis than Cx43-forming gap junctions was investigated by generating mutant granulosa cells, which can form hemichannels, but no functional gap junctions [131].…”

Section: Implications For Oogenesismentioning

confidence: 99%

Physiological roles of connexins and pannexins in reproductive organs

Kibschull

Gellhaus

Carette

et al. 2015

Cell. Mol. Life Sci.

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Reproductive organs are complex and well-structured tissues essential to perpetuate the species. In mammals, the male and female reproductive organs vary on their organization, morphology and function. Connectivity between cells in such tissues plays pivotal roles in organogenesis and tissue functions through the regulation of cellular proliferation, migration, differentiation and apoptosis. Connexins and pannexins can be seen as major regulators of these physiological processes. In the present review, we assembled several lines of evidence demonstrating that these two families of proteins are essential for male and female reproduction.

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“…The Cx32 siRNA duplexes also significantly (p \ 0.05) lowered extracellular ATP release by hepatocytes to 65.1 ± 7.5% of the control level following withdrawal of divalent ions from the cell culture medium (Fig. 7d), which is a well-known protocol to trigger hemichannel opening and thus to measure their functionality [30][31][32].…”

Section: Effects Of Cx32 Sirna On Cell Death Induced By Fasl/chxmentioning

confidence: 99%

“…To substantiate this anticipated role for hepatocellular Cx32-originating connexons, we used 32 Gap27, a short peptide that mimics a sequence in the second extracellular loop of the Cx32 subunit. Previous research showed that shortterm incubations (0.5-6.5 h) with connexin mimetic peptides are sufficient to inhibit hemichannel-related responses, i.e., low extracellular divalent ion-triggered cellular ATP release, in a connexin-specific way, whereas longer exposure regimes (24 h) also result in the reduction of corresponding GJIC [31,32]. In agreement with this finding, 6.5 h exposure (i.e., 0.5 h pre-incubation followed by 6 h exposure, as required to complete the cell death response) of the hepatocytes to 32 Gap27 (0.25 mg/ ml) significantly (p \ 0.05) reduced the ATP release triggered by divalent ion depletion to 62.4 ± 4.8% of the initial level (Fig.…”

Section: Effects Of Cx32 Mimetic Peptide On Cell Death Induced By Fasmentioning

confidence: 99%

Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death

Vinken

Decrock

Vuyst

et al. 2009

Cell. Mol. Life Sci.

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The present study was set up to investigate the fate of connexin32 and its channels in hepatocellular apoptosis. Primary hepatocyte cultures were exposed to Fas ligand and cycloheximide, and modifications in connexin32 expression and localization, and gap junction functionality were studied. We found that gap junction functionality rapidly declined upon progression of cell death, which was associated with a decay of the gap junctional connexin32 protein pool. Simultaneously, levels of newly synthesized connexin32 protein increased and gathered in a hemichannel configuration. This became particularly evident towards the end stages of the cell death process and was not reflected at the transcriptional level. We next either silenced connexin32 expression or inhibited connexin32 hemichannel activity prior to cell death induction. Both approaches resulted in a delayed termination of the cell death response. We conclude that connexin32 hemichannels facilitate the apoptotic-to-necrotic transition, which typically occurs in the final stage of hepatocellular apoptosis.

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Connexin Channels, Connexin Mimetic Peptides and ATP Release

Cited by 38 publications

References 0 publications

Connexin 43 mimetic peptide Gap26 confers protection to intact heart against myocardial ischemia injury

Connexin 43 mimetic peptide Gap26 confers protection to intact heart against myocardial ischemia injury

Physiological roles of connexins and pannexins in reproductive organs

Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death

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