TNF-α-Induced cPLA2 Expression via NADPH Oxidase/Reactive Oxygen Species-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

With wide application of Zinc oxide (ZnO) nanoparticles, their biological toxicity has received more and more attention in recent years. In this research, two ZnO dispersions with different particle sizes, small size Zinc oxide (S-ZnO) and big size Zinc oxide (B-ZnO), were prepared using polycarboxylic acid as dispersant. We found that the S-ZnO nanoparticles showed stronger toxicity on Human Pulmonary Alveolar Epithelial Cells (HPAEpiC) under same concentration. Only 9 ppm S-ZnO could decrease HPAEpiC viability to about 50%, which means that, a small amount of well-dispersed ZnO nanoparticles in industrial production process may cause serious damage to the human body through oral inhalation. Focusing on mechanism for cytotoxicity, ZnO nanoparticles promoted generation and accumulation of Reactive Oxygen Species (ROS) in mitochondria via inhibiting Superoxide Dismutase (SOD) enzyme activity and reducing Glutathione (GSH) content. ROS in turn opened the mitochondrial Ca2+ pathway and lowered the Mitochondrial Membrane Potentials (MMP), leading to cell death. To simulate the lung environment in vitro, mixed dipalmitoyl phosphatidylcholine (DPPC) and ZnO nanoparticles (1:1) were incubated for 72 hours and then cytotoxicity was evaluated on HPAEpiC. Results showed that the cell viability was significantly increased, which proved that the DPPC effectively inhibited the toxicity of ZnO nanoparticles.

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Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01001.2001 ◽

2002 ◽

Vol 283 (5) ◽

pp. H2054-H2061 ◽

Cited By ~ 50

Author(s):

Manabu Takano ◽

Avedis Meneshian ◽

Emran Sheikh ◽

Yasuhiko Yamakawa ◽

Kirsten Bass Wilkins ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Xanthine Oxidase ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

Tnf Α ◽

Early Peak ◽

New Protein

Endothelial cell ICAM-1 upregulation in response to TNF-α is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase. We found that this rapid expression of P-selectin on the surface of endothelial cells was accompanied by qualitatively parallel increases in ROS generation. Both P-selectin expression and ROS generation were inhibited, dose dependently, by the exogenous administration of disparate cell-permeable antioxidants and also by the inhibition of either of the known membrane-associated ROS-generating enzymes NADPH oxidase or xanthine oxidase. This rapid, posttranslational cell signaling response, mediated by ROS generated not only by the classical NADPH oxidase but also by xanthine oxidase, may well represent an important physiological trigger of the microvascular inflammatory response.

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nNOS and Nox4 go nuclear: nNOS-derived and NADPH oxidase-derived reactive oxygen/nitrogen species promote oxidative nuclear damage in alveolar epithelial cells

Critical Care ◽

10.1186/cc5177 ◽

2007 ◽

Vol 11 (Suppl 2) ◽

pp. P17

Author(s):

R Connelly ◽

F Schmalstieg ◽

D Traber

Keyword(s):

Epithelial Cells ◽

Nadph Oxidase ◽

Reactive Oxygen ◽

Alveolar Epithelial Cells ◽

Nitrogen Species ◽

Alveolar Epithelial ◽

Nuclear Damage

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Production of Reactive Oxygen Species Is Turned On and Rapidly Shut Down in Epithelial Cells Infected with Chlamydia trachomatis

Infection and Immunity ◽

10.1128/iai.00725-09 ◽

2009 ◽

Vol 78 (1) ◽

pp. 80-87 ◽

Cited By ~ 38

Author(s):

Gaëlle Boncompain ◽

Benoît Schneider ◽

Cédric Delevoye ◽

Odile Kellermann ◽

Alice Dautry-Varsat ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Chlamydia Trachomatis ◽

Epithelial Cells ◽

Nadph Oxidase ◽

Reactive Oxygen ◽

Regulatory Subunit ◽

Developmental Cycle ◽

Ros Production ◽

Oxygen Species ◽

Cell Defense

ABSTRACT Reactive oxygen species (ROS) are many-faceted compounds involved in cell defense against pathogens, as well as in cell signaling. Their involvement in the response to infection in epithelial cells remains poorly documented. Here, we investigated the production of ROS during infection with Chlamydia trachomatis, a strict intracellular pathogen, in HeLa cells. C. trachomatis induced a transient increase in the ROS level within a few hours, followed by a return to basal level 9 hours after infection. At this time point, the host enzyme dedicated to ROS production, NADPH oxidase, could no longer be activated by external stimuli, such as interleukin-1β. In addition, Rac, a regulatory subunit of the NADPH oxidase complex, was relocated to the membrane of the compartment in which the bacteria develop, the inclusion, while other subunits were not. Altogether, these results indicate that C. trachomatis infection elicits the production of ROS and that the bacteria rapidly target the activity of NADPH oxidase to shut it down. Prevention of ROS production at the onset of the bacterial developmental cycle might delay the host response to infection.

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Mitochondrial DNA-depleted A549 cells are resistant to bleomycin

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00343.2011 ◽

2012 ◽

Vol 303 (5) ◽

pp. L413-L424 ◽

Cited By ~ 22

Author(s):

Sukhdev S. Brar ◽

Joel N. Meyer ◽

Carl D. Bortner ◽

Bennett Van Houten ◽

William J. Martin

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Mitochondrial Dna ◽

Molecular Mechanisms ◽

Caspase 3 ◽

A549 Cells ◽

Reactive Oxygen ◽

Alveolar Epithelial Cells ◽

Oxygen Species ◽

Alveolar Epithelial

Alveolar epithelial cells are considered to be the primary target of bleomycin-induced lung injury, leading to interstitial fibrosis. The molecular mechanisms by which bleomycin causes this damage are poorly understood but are suspected to involve generation of reactive oxygen species and DNA damage. We studied the effect of bleomycin on mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) in human alveolar epithelial A549 cells. Bleomycin caused an increase in reactive oxygen species production, DNA damage, and apoptosis in A549 cells; however, bleomycin induced more mtDNA than nDNA damage. DNA damage was associated with activation of caspase-3, cleavage of poly(ADP-ribose) polymerase, and cleavage and activation of protein kinase D1 (PKD1), a newly identified mitochondrial oxidative stress sensor. These effects appear to be mtDNA-dependent, because no caspase-3 or PKD1 activation was observed in mtDNA-depleted (ρ0) A549 cells. Survival rate after bleomycin treatment was higher for A549 ρ0 than A549 cells. These results suggest that A549 ρ0 cells are more resistant to bleomycin toxicity than are parent A549 cells, likely in part due to the depletion of mtDNA and impairment of mitochondria-dependent apoptotic pathways.

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