Reversible inhibition of intercellular junctional communication by glycyrrhetinic acid

Davidson, James S.; Baumgarten, Ingrid; Harley, Eric H.

doi:10.1016/0006-291x(86)90522-x

Cited by 280 publications

(237 citation statements)

References 12 publications

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“…2A), a GJ blocker (10,16). After blocker wash out (3 washes of 1 min each), rapid recovery to the original incidence of dye coupling was observed ( Fig.…”

Section: Treatment With Lps Plus Ifn-γ Induces Intercellular Communicmentioning

confidence: 92%

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Eugenín

González

Sánchez

et al. 2007

Cellular Immunology

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Connexin43 (Cx43), a gap junction protein subunit, has been previously detected in Kupffer cells (KCs) during liver inflammation, however, KCs phagocytose cell debris that may include Cx43 protein, which could explain the detection of Cx43 in KCs. We determined that KCs express Cx43 and form gap junctions both in vivo and in vitro. In liver sections of animals treated with LPS, Cx43 was detected at ED2+ cells interfaces, indicating formation of GJ between KCs in vivo. In vitro, unstimulated KCs cultures did not form functional GJs, and expressed low levels of Cx43 that showed a diffuse intracellular distribution. In contrast, KCs treated with LPS plus IFN-γ, expressed a greater amount of Cx43 at both the, protein and mRNA levels, and showed Cx43 at cell-cell contacts associated with higher dye coupling. In conclusion, activation of KCs in vivo or in vitro resulted in enhanced Cx43 expression levels and formation of GJ that might play relevant roles during liver inflammation.

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“…2A), a GJ blocker (10,16). After blocker wash out (3 washes of 1 min each), rapid recovery to the original incidence of dye coupling was observed ( Fig.…”

Section: Treatment With Lps Plus Ifn-γ Induces Intercellular Communicmentioning

confidence: 92%

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Eugenín

González

Sánchez

et al. 2007

Cellular Immunology

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“…The inhibition mediated by 18--glycyrrhetinic acid was dose dependent and the maximum effect was observed at a concentration of 50 M, consistent with previous studies. 11 No inhibition was observed if 18 --glycyrrhetinic acid was replaced by its inactive isomer, glycyrrhizic acid (Fig 4 ). Figure 4 The inhibition of gap junctions by 18 --glycyrrhetinic acid abolishes the bystander effect in a coculture of TK + ( 30% ) and TK À ( 70% ) CNS1 cells.…”

Section: Cx43 Expression and Gap Junctional Communicationmentioning

confidence: 97%

“…10 The doses and duration of GCV treatment were determined in preliminary experiments on CNS1 -TK + and C6 -TK + cells ( data not shown). To block gap junctions, we added 18--glycyrrhetinic acid, an inhibitor of gap junction permeability, or glycyrrhizic acid, an inactive isomer, 11 at various concentrations ( range 0-200 M) to the wells containing mixtures of TK + and TK À cells.…”

Section: Plasmid Constructionmentioning

confidence: 99%

Connexin 43–mediated bystander effect in two rat glioma cell models

et al. 2002

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In tumor models, the killing by ganciclovir of a fraction of tumor cells transfected with the thymidine kinase ( TK ) gene has been shown to induce complete regression of the tumor. The mechanism responsible for this bystander effect is thought to be the diffusion of toxic metabolites or apoptotic signals across gap junctions. Connexin 43 ( Cx43 ) is the major component of astrocyte gap junctions. We investigated the susceptibility of two rat glioma cell lines ( CNS1 and C6 ) to thymidine kinase / ganciclovir, before and after transfection with the Cx43 gene. We report a close correlation between the level of Cx43 expression, the extent of gap junctional communication and the amplitude of the bystander effect. Transfection of C6 cells ( which display a weak bystander effect and low levels of connexin ) with a Cx43 construct induced a strong bystander effect. Inhibition of gap junction activity by 18 --glycyrrhetinic acid abolished the metabolic interaction between TK + and TK À cells. This metabolic interaction was also abolished if TK + and TK À cells were separated by a semipermeable membrane. Surprisingly, the transfection of only one of these two interacting cell types with the Cx43 gene was sufficient to induce a bystander effect, although this effect was weaker than that observed if both TK + and TK À cells expressed Cx43. Finally, Cx43 expression increased sensitivity to contact inhibition. Overall, our data provide evidence that the restoration of gap junctional communication may potentiate HSV / tk -based cancer treatment and suggest that this strategy may have wider application in cancer therapy.

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“…After application of 1 μM BGA, responsiveness of Neuron A to octaldehyde was reduced to threshold levels (Phase 2A). Since the effect of BGA is reversible [46,47], Neuron A regained its response magnitude to octaldehyde minutes later (Phase 3A). Phase 4A in Figure 4 shows that responsiveness of Neuron A to IBMX was not influenced by application of BGA.…”

Section: Resultsmentioning

confidence: 99%

Gap junctions in olfactory neurons modulate olfactory sensitivity

Zhang

2010

BMC Neurosci

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BackgroundOne of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis.ResultsI generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited c-fos mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons.ConclusionsMy study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory sensitivity and odor perception.

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Reversible inhibition of intercellular junctional communication by glycyrrhetinic acid

Cited by 280 publications

References 12 publications

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Connexin 43–mediated bystander effect in two rat glioma cell models

Gap junctions in olfactory neurons modulate olfactory sensitivity

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