The role of pulmonary ORCC and CLC-2 channels in the response to oxidative stress

Abstract Background Exposure of human lung epithelial cells to the oxidant pollutant ozone (O3) alters cell Cl− currents inducing an outward rectifier effect. Among the various Cl− channels, ClC-2 and ORCC seemed to be involved in this response. Objectives To identify the channel related to O3 induced current changes. Results Down regulating the expression of ORCC and ClC-2 genes and analyzing the membrane current show that the enhancement of the current disappeared when ORCC was silenced. The contribution of ORCC and ClC-2 channels in control and O3 treated cells was obtained by a mathematical approach. Conclusion We suggest that O3 activates ORCC channels and slightly inhibited ClC-2 channels in the negative voltage range. These findings open the possibility of identifying the biomolecular changes induced by O3 allowing a possible pharmacological intervention towards chloride current due to oxidative stress.

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Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage

Environmental Pollution ◽

10.1016/j.envpol.2021.116969 ◽

2021 ◽

Vol 281 ◽

pp. 116969

Author(s):

Sourav Kumar Das ◽

Manjoor Ali ◽

Neena G. Shetake ◽

Rama Mohan R. Dumpala ◽

Badri N. Pandey ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Human Lung ◽

Lung Epithelial Cells ◽

Thorium Nitrate ◽

Thorium Dioxide ◽

Lung Epithelial ◽

Normal Human ◽

Human Lung Epithelial Cells

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Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: Role of the specific surface area and of surface methylation of the particles

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2007.05.001 ◽

2007 ◽

Vol 222 (2) ◽

pp. 141-151 ◽

Cited By ~ 245

Author(s):

S SINGH ◽

T SHI ◽

R DUFFIN ◽

C ALBRECHT ◽

D VANBERLO ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Specific Surface ◽

Surface Area ◽

Human Lung ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Ultrafine Tio2 ◽

Human Lung Epithelial Cells

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Oxidative stress–inducing effects of various urban PM2.5 road dust on human lung epithelial cells among 10 Chinese megacities

Ecotoxicology and Environmental Safety ◽

10.1016/j.ecoenv.2021.112680 ◽

2021 ◽

Vol 224 ◽

pp. 112680

Author(s):

Jian Sun ◽

Jinjin Yu ◽

Zhenxing Shen ◽

Xinyi Niu ◽

Diwei Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Human Lung ◽

Road Dust ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Human Lung Epithelial Cells

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A model to identify novel targets involved in oxidative stress-induced apoptosis in human lung epithelial cells by RNA interference

Toxicology in Vitro ◽

10.1016/j.tiv.2009.08.008 ◽

2010 ◽

Vol 24 (1) ◽

pp. 310-318 ◽

Cited By ~ 3

Author(s):

William E. Wixted ◽

Chris Kitson ◽

Jayne C. Colebrook ◽

Emma J. Roberts ◽

Steven M. Fox ◽

...

Keyword(s):

Oxidative Stress ◽

Rna Interference ◽

Epithelial Cells ◽

Human Lung ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Novel Targets ◽

Induced Apoptosis ◽

Human Lung Epithelial Cells

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Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.13221 ◽

2019 ◽

Vol 125 (3) ◽

pp. 304-314 ◽

Cited By ~ 3

Author(s):

Magne Refsnes ◽

Tonje Skuland ◽

Edel Lilleaas ◽

Johan Øvrevik ◽

Marit Låg

Keyword(s):

Epithelial Cells ◽

Silica Nanoparticles ◽

Human Lung ◽

Lung Epithelial Cells ◽

Cytokine Responses ◽

Lung Epithelial ◽

Human Lung Epithelial Cells

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Regulation of apoptosis by Bcl-2 cysteine oxidation in human lung epithelial cells

Molecular Biology of the Cell ◽

10.1091/mbc.e12-10-0747 ◽

2013 ◽

Vol 24 (6) ◽

pp. 858-869 ◽

Cited By ~ 43

Author(s):

Sudjit Luanpitpong ◽

Pithi Chanvorachote ◽

Christian Stehlik ◽

William Tse ◽

Patrick S. Callery ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Human Lung ◽

Critical Role ◽

B Cell Lymphoma ◽

Lung Epithelial Cells ◽

Mitogen Activated Protein Kinase ◽

Cysteine Oxidation ◽

Lung Epithelial ◽

Human Lung Epithelial Cells

Hydrogen peroxide is a key mediator of oxidative stress known to be important in various cellular processes, including apoptosis. B-cell lymphoma-2 (Bcl-2) is an oxidative stress–responsive protein and a key regulator of apoptosis; however, the underlying mechanisms of oxidative regulation of Bcl-2 are not well understood. The present study investigates the direct effect of H2O2on Bcl-2 cysteine oxidation as a potential mechanism of apoptosis regulation. Exposure of human lung epithelial cells to H2O2induces apoptosis concomitant with cysteine oxidation and down-regulation of Bcl-2. Inhibition of Bcl-2 oxidation by antioxidants or by site-directed mutagenesis of Bcl-2 at Cys-158 and Cys-229 abrogates the effects of H2O2on Bcl-2 and apoptosis. Immunoprecipitation and confocal microscopic studies show that Bcl-2 interacts with mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2 [ERK1/2]) to suppress apoptosis and that this interaction is modulated by cysteine oxidation of Bcl-2. The H2O2-induced Bcl-2 cysteine oxidation interferes with Bcl-2 and ERK1/2 interaction. Mutation of the cysteine residues inhibits the disruption of Bcl-2–ERK complex, as well as the induction of apoptosis by H2O2. Taken together, these results demonstrate the critical role of Bcl-2 cysteine oxidation in the regulation of apoptosis through ERK signaling. This new finding reveals crucial redox regulatory mechanisms that control the antiapoptotic function of Bcl-2.

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