<i>S</i>‐Carbocysteine‐lysine salt monohydrate and cAMP cause non‐additive activation of the cystic fibrosis transmembrane regulator channel in human respiratory epithelium

Meyer, Gerd; Doppierio, Sonia; Daffonchio, L.; Cremaschi, D.

doi:10.1016/s0014-5793(97)00074-4

Cited by 9 publications

(10 citation statements)

References 21 publications

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“…As still suggested [7,32], this datum confirmed that the S-CMC-Lys-stimulated currents were dependent on CFTR activity. The CFTR-mediated GSH and chloride currents, which were maximally activated after S-CMC-Lys treatment [9], were not significantly inhibited after 1 μM H 2 O 2 and 10…”

Section: Discussionmentioning

confidence: 90%

“…The expression of CFTR in these cells had been verified by Western Blot experiments [7] and by PCR amplification after reverse transcription followed by Southern hybridization [10]. The presence of a functional CFTR channel in the plasma membrane of WI26-VA4 cells had been evidenced by patch-clamp experiments both in cell-attached and in wholecell configuration [7,9].…”

Section: Methodsmentioning

confidence: 97%

“…WI-26VA4 cells, which were already used to test S-CMC-lys effects [7,9], are an SV40 virus transformed derivative of WI-26, a human cell line from embryonic lung tissue that underwent to a change in morphology towards "epithelial-like" cells, after SV40 transformation. The expression of CFTR in these cells had been verified by Western Blot experiments [7] and by PCR amplification after reverse transcription followed by Southern hybridization [10].…”

Section: Methodsmentioning

confidence: 99%

“…A Mg 2+ -free, theophylline-containing intracellular solution was used to slow down CFTR channel rundown [13][14][15]. The existence, in S-CMC-Lys-incubated cells, of a functionally active CFTR channel had been verified both in excised and in whole-cell experiments [7,9].…”

Section: Electrophysiological Measurementsmentioning

confidence: 99%

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S-CMC-Lys Protective Effects on Human Respiratory Cells During Oxidative Stress

Garavaglia

Bononi

Dossena

et al. 2008

Cell Physiol Biochem

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The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys) stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of the most important redox regulatory mechanisms, the aim of this study was to evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration during an oxidative stress induced by the hydroxyl radical (•OH). Experiments were performed on cultured human respiratory WI-26VA4 cells by means of patch-clamp experiments in whole-cell configuration and of fluorimetric analyses at confocal microscope. •OH exposure induced an irreversible inhibition of the GSH and chloride currents that was prevented if the cells were incubated with S-CMC-Lys. In this instance, the currents were inhibited by the specific blocker CFTR_inh-172. CFT1-C2 cells, which lack a functional CFTR channel, were not responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric measurements performed on the S-CMC-Lys-incubated cells revealed a significant increase of the GSH concentration that was completely hindered after oxidative stress and abolished by CFTR_inh-172. The cellular content of reactive oxygen species was significantly lower in the S-CMC-Lys-treated cells either before or after •OH exposure. As a conclusion, S-CMC-Lys could exert a protective function during oxidative stress, therefore preventing or reducing the ROS-mediated inflammatory response.

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Section: Discussionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Electrophysiological Measurementsmentioning

confidence: 99%

See 2 more Smart Citations

S-CMC-Lys Protective Effects on Human Respiratory Cells During Oxidative Stress

Garavaglia

Bononi

Dossena

et al. 2008

Cell Physiol Biochem

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“…This is a complex phenomenon, however, since the activation appears to also require low-level constitutive phosphorylation of CFTR by protein kinase C (PKC) [8]. In addition, the activity is influenced by several modulators [2,9,11]. Thus in a number of recent publications evidence has been presented that genistein, an inhibitor of protein tyrosine kinases (PTK) [1] and probably of protein phosphatases (PPase), potentiates PKA-mediated activation of the CFTR Cl -channel in various cell culture models [5,6,7,12,13,14,17,18,19].…”

Section: Introductionmentioning

confidence: 99%

The activation of an apical Cl– conductance by extracellular ATP is potentiated by genistein in Necturus gallbladder epithelium

Vank

Frömter

Kottra

1999

Pflügers Arch – Eur J Physiol

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Necturus gallbladder epithelium (NGE) expresses a CFTR-homologous apical Cl- conductance (Ga,Cl) which can be activated either by elevation of intracellular cAMP or by extracellular ATP. Here we show by microelectrode experiments and impedance analysis that genistein (50 microM), which is known to potentiate the stimulation of Ga,Cl in several cell culture models, also potentiates the stimulation of Ga,Cl by low doses of forskolin in NGE. Moreover, we show that genistein also potentiates the stimulation of Ga,Cl by ATP. In addition genistein renders gallbladders that initially do not respond to ATP sensitive to this stimulant, and it delays the conductance inactivation after ATP removal. Under control conditions Ga,Cl inactivates within < 5 min, but in the presence of genistein a significant Ga,Cl persists even after 60 min. These effects of genistein are not related to inhibition of protein tyrosine kinases, since structurally different inhibitors of the tyrphostin family do not mimic the genistein effects. The data support our conclusion that stimulation of Ga,Cl by ATP is mediated by activation of the cAMP pathway and involves a CFTR-homologous protein. They also favour the view that genistein acts via inhibition of protein phosphatases which dephosphorylate CFTR, but cannot exclude the possibility of a direct interaction with CFTR.

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Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells

et al. 2019

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Objective: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture.Methods: The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera.Results: CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl − concentration ([Cl − ] i ) in cHNECs. The CCis' actions were mimicked by the Cl − -free NO 3 − solution. In contrast, prior treatment of NPPB (20 μM) or CFTR(inh)-172 (1 μM), which increased [Cl − ] i by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 μM) did not inhibit the CCis' actions, although it decreased [Cl -] i by 10% and CBD by 15%. Thus, CCis stimulates Clchannels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints.Conclusion: CCis increased CBD by 30% in cHNECs via an [Cl − ] i decrease stimulated by activation of Cl − channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR.

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S‐Carbocysteine‐lysine salt monohydrate and cAMP cause non‐additive activation of the cystic fibrosis transmembrane regulator channel in human respiratory epithelium

Cited by 9 publications

References 21 publications

S-CMC-Lys Protective Effects on Human Respiratory Cells During Oxidative Stress

S-CMC-Lys Protective Effects on Human Respiratory Cells During Oxidative Stress

The activation of an apical Cl– conductance by extracellular ATP is potentiated by genistein in Necturus gallbladder epithelium

Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells

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