scholarly journals Mitochondrial DNA-depleted A549 cells are resistant to bleomycin

2012 ◽  
Vol 303 (5) ◽  
pp. L413-L424 ◽  
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.

scholarly journals Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles

2012 ◽  
Vol 215 (3) ◽  
pp. 151-160 ◽  
Author(s):  
Kunal Bhattacharya ◽  
Pratap C. Naha ◽  
Izabela Naydenova ◽  
Svetlana Mintova ◽  
Hugh J. Byrne
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Human Lung ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Alveolar Epithelial ◽  
Type Zeolite

The role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species

2011 ◽  
Vol 43 (1) ◽  
pp. 25-29 ◽  
Author(s):  
R. A. P. Costa ◽  
C. D. Romagna ◽  
J. L. Pereira ◽  
N. C. Souza-Pinto
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Dna Damage

Mitochondrial DNA damage and altered membrane potential (ΔΨ) in pancreatic acinar cells induced by reactive oxygen species

Surgery ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Richard A. Ehlers ◽  
Ambrosio Hernandez ◽  
L.Scott Bloemendal ◽  
Richard T. Ethridge ◽  
Buckminster Farrow ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Membrane Potential ◽  
Reactive Oxygen ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Oxygen Species ◽  
Mitochondrial Dna Damage

scholarly journals Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Sun ◽  
Tongsheng Chen ◽  
Xiaoping Wang ◽  
Yun Chen ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Temporal Dynamics ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

scholarly journals Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage

2004 ◽  
Vol 124 (0) ◽  
pp. 16-24 ◽  
Author(s):  
Michael Seidman ◽  
Nadir Ahmad ◽  
Dipa Joshi ◽  
Jake Seidman ◽  
Sujatha Thawani ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Hearing Loss ◽  
Mitochondrial Dna ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Dna Damage ◽  
Age Related ◽  
Age Related Hearing Loss

Low Concentrations of Zinc Oxide Nanoparticles Cause Severe Cytotoxicity Through Increased Intracellular Reactive Oxygen Species

2021 ◽  
Vol 17 (12) ◽  
pp. 2420-2432
Author(s):  
Shichen Xie ◽  
Jingyao Zhu ◽  
Dicheng Yang ◽  
Yan Xu ◽  
Jun Zhu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Zinc Oxide ◽  
Zno Nanoparticles ◽  
Reactive Oxygen ◽  
Alveolar Epithelial Cells ◽  
Oxygen Species ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Alveolar Epithelial ◽  
Low Concentrations

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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