Lipidated connexin mimetic peptides potently inhibit gap junction-mediated Ca2+-wave propagation.

  title={Lipidated connexin mimetic peptides potently inhibit gap junction-mediated Ca2+-wave propagation.},
  author={Mary Lou Cotter and Scott A. Boitano and Josef Vagner and Janis M Burt},
  journal={American journal of physiology. Cell physiology},
  volume={315 2},
Connexin (Cx) mimetic peptides (e.g., Gap27: SRPTEKTIFII; Peptide5: VDCFLSRPTEKT) reversibly inhibit hemichannel (HCh) and gap junction channel (GJCh) function in a concentration- and time-dependent manner (HCh: ~5 µM, <1 h; GJCh: ~100 µM, > 1 h). We hypothesized that addition of a hexadecyl tail to SRPTEKT (SRPTEKT- Hdc) would improve its ability to concentrate in the plasma membrane and consequently increase its inhibitory efficacy. We show that SRPTEKT- Hdc inhibited intercellular Ca2+-wave… 
The lipidated connexin mimetic peptide, SRPTEKT-Hdc, is a potent inhibitor of Cx43 channels with specificity for the pS368 phospho-isoform.
Adding a hexadecyl (Hdc) lipid tail to the conserved SRPTEKT peptide sequence results in a novel, highly efficacious and potent inhibitor of mechanically-induced Ca2+-wave propagation and dye uptake in Madin-Darby canine kidney cells expressing rCx43 (MDCK43).
Therapeutic Targeting of Connexin Channels: New Views and Challenges.
A critical overview on the use of connexin-targeting peptides, in particular targeting Cx43, is provided, with a special focus on the remaining questions and hurdles to be taken in the research field of con Nexin channels.
Mechanisms of Connexin Mimetic Peptides
Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies
Mechanisms of Connexin Regulating Peptides
This overview of published connexin targeting peptides, their reported mechanisms of action, and the potential for these molecules in the treatment of disease is discussed.
Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide.
The synthesis and biological activity of 42 novel S-lipidated analogues of a connexin 43 channel inhibitory Peptide5 is described. Unmodified Peptide5 moderates hemichannels and gap junctions that
Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine
Preclinical and clinical data available on short mimetic peptides based on, or directly targeting, Cx43, with focus on their potential for treating heart disease are surveyed and problems that have caused reluctance within the pharmaceutical industry to translate peptidic therapeutics to the clinic are discussed.
Targeting gap junction in epilepsy: Perspectives and challenges.
Targeting GJs is likely to be served as a novel therapeutic approach on epileptic patients and exert potent curative potential on epilepsy in vivo or in vitro.
Cardiac Conduction Velocity, Remodeling and Arrhythmogenesis
Methods to measure cardiac CV in vivo and ex vivo are examined, underlying determinants of CV are discussed, and how pathological variations alter CV is addressed, potentially increasing arrhythmogenic risk.


Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation
Results indicate that under pathological conditions, when [Ca2+]i is elevated, Cx43 HC opening is promoted in cardiomyocytes and CxMPs counteract this effect.
Gap26, a connexin mimetic peptide, inhibits currents carried by connexin43 hemichannels and gap junction channels.
The results support the view that the likely primary and direct inhibitory effect of Gap26 is on connexin hemich channels, with gap junctions becoming inhibited later, and the mechanism of action of Gap 26 in blocking hemichannels and gap junction channels is discussed.
Connexin mimetic peptides reversibly inhibit Ca(2+) signaling through gap junctions in airway cells.
  • S. Boitano, W. H. Evans
  • Biology, Medicine
    American journal of physiology. Lung cellular and molecular physiology
  • 2000
It is concluded that connexin mimetic peptides are effective and reversible inhibitors of gap junctional communication of physiologically significant molecules that underlie Ca(2+) wave propagation in tracheal epithelial cells and a potential mechanism for the mode of action is proposed.
Mimetic Peptides as Blockers of Connexin Channel-Facilitated Intercellular Communication
A mechanism is proposed to help explain the dual action of connexin mimetic peptides on con Nexin hemichannels and gap-junctional coupling.
Characterizing the mode of action of extracellular Connexin43 channel blocking mimetic peptides in an in vitro ischemia injury model.
The concentration dependent and sequence specific action of Peptide5 supports its development for the treatment of retinal injury and chronic disease, as well as other central nervous system injury and disease conditions.
Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury
It is concluded that preventing Cx43 hemichannel opening with Gap19 confers limited protective effects against myocardial ischemia/reperfusion injury.
Connexin mimetic peptides: specific inhibitors of gap-junctional intercellular communication.
Connexin mimetic peptides that correspond to short specific sequences in the two extracellular loops of connexins are a class of benign, specific and reversible inhibitors of gap-junctional communication that have been studied recently in a broad range of cells, tissues and organs.
The Connexin Mimetic Peptide Gap27 and Cx43-Knockdown Reveal Differential Roles for Connexin43 in Wound Closure Events in Skin Model Systems
Connexin43 signalling plays an important role in cell migration in keratinocytes and foreskin derived fibroblasts, however, different pathways are evoked and in dermal derived adult and neonatal fibro Blasts, inhibition of Connexin 43 signalling plays a more significant role in regulating cell proliferation than cell migration.
Ca(2+) regulation of connexin 43 hemichannels in C6 glioma and glial cells.
Hemichannel opening is triggered not by a direct action of Ca(2+) on hemichannels but via multiple intermediate signaling steps that are adjoined by distinct signaling mechanisms activated by high [Ca(2+)](i) and acting to restrain cellular ATP loss.
Cx43 Hemichannels and Gap Junction Channels in Astrocytes Are Regulated Oppositely by Proinflammatory Cytokines Released from Activated Microglia
It is demonstrated that either conditioned medium harvested from activated microglia or a mixture of these two cytokines enhances the cellular exchange with the extracellular milieu via Cx43 hemichannels, which opposite regulation may affect glucose trafficking and certainly will modify the metabolic status of astrocytes involved in brain inflammation.