Airborne quinones induce cytotoxicity and DNA damage in human lung epithelial A549 cells: The role of reactive oxygen species

Idiopathic pulmonary fibrosis (IPF) is a pernicious lung disease characterized by alveolar epithelial apoptosis, dysregulated repair of epithelial injury, scar formation, and respiratory failure. In this study, we identified phospholipase D (PLD)-generated phosphatidic acid (PA) signaling in the development of pulmonary fibrosis (PF). Of the PLD isoenzymes, the protein expression of PLD2, but not PLD1, was upregulated in lung tissues from IPF patients and bleomycin challenged mice. Both PLD1 ( Pld1−/−)- and PLD2 ( Pld2−/−)-deficient mice were protected against bleomycin-induced lung inflammation and fibrosis, thereby establishing the role of PLD in fibrogenesis. The role of PLD1 and PLD2 in bleomycin-induced lung epithelial injury was investigated by infecting bronchial airway epithelial cells (Beas2B) with catalytically inactive mutants of PLD ( hPLD1-K898R or mPld2-K758R) or downregulation of expression of PLD1 or PLD2 with siRNA. Bleomycin stimulated mitochondrial (mt) superoxide production, mtDNA damage, and apoptosis in Beas2B cells, which was attenuated by the catalytically inactive mutants of PLD or PLD2 siRNA. These results show a role for PLD1 and PLD2 in bleomycin-induced generation of mt reactive oxygen species, mt DNA damage, and apoptosis of lung epithelial cells in mice. Thus, PLD may be a novel therapeutic target in ameliorating experimental PF in mice.

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

Journal of Bioenergetics and Biomembranes ◽

10.1007/s10863-011-9329-8 ◽

2011 ◽

Vol 43 (1) ◽

pp. 25-29 ◽

Cited By ~ 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

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Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

Antioxidants and Redox Signaling ◽

10.1089/ars.2008.2203 ◽

2009 ◽

Vol 11 (4) ◽

pp. 747-764 ◽

Cited By ~ 122

Author(s):

Srikanth Pendyala ◽

Irina A Gorshkova ◽

Peter V. Usatyuk ◽

Donghong He ◽

Arjun Pennathur ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Human Lung ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Lung Endothelial Cells ◽

And Migration

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Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related catecholamine neurotransmitters and neurotoxins: Role of reactive oxygen species

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2010.10.693 ◽

2011 ◽

Vol 50 (1) ◽

pp. 139-147 ◽

Cited By ~ 48

Author(s):

Wendy A. Spencer ◽

Jeyaprakash Jeyabalan ◽

Sunita Kichambre ◽

Ramesh C. Gupta

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Reactive Oxygen ◽

Oxygen Species

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Mycoplasma pneumoniae Infection Induces Reactive Oxygen Species and DNA Damage in A549 Human Lung Carcinoma Cells

Infection and Immunity ◽

10.1128/iai.00575-08 ◽

2008 ◽

Vol 76 (10) ◽

pp. 4405-4413 ◽

Cited By ~ 39

Author(s):

Gongping Sun ◽

Xuefeng Xu ◽

Yingshuo Wang ◽

Xiaoyun Shen ◽

Zhimin Chen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Mycoplasma Pneumoniae ◽

Lung Carcinoma ◽

Human Lung ◽

Reactive Oxygen ◽

Carcinoma Cells ◽

Oxygen Species ◽

Lung Carcinoma Cells ◽

Human Lung Carcinoma

ABSTRACT Mycoplasma pneumoniae is a frequent cause of community-acquired bacterial respiratory infections in children and adults. In the present study, using a proteomic approach, we studied the effects of M. pneumoniae infection on the protein expression profile of A549 human lung carcinoma cells. M. pneumoniae infection induced changes in the expression of cellular proteins, in particular a group of proteins involved in the oxidative stress response, such as glucose-6-phosphate 1-dehydrogenase, NADH dehydrogenase (ubiquinone) Fe-S protein 2, and ubiquinol-cytochrome c reductase complex core protein I mitochondrial precursor. The oxidative status of M. pneumoniae-infected cells was evaluated, and the results revealed that M. pneumoniae infection indeed caused generation of reactive oxygen species (ROS). It was further shown that M. pneumoniae infection also induced DNA double-strand breaks, as demonstrated by the formation of γH2AX foci. On the other hand, an ROS scavenger, N-acetylcysteine, could inhibit the ROS generation, as well as decrease γH2AX focus formation. This is the first report showing that M. pneumoniae infection can directly induce DNA damage, at least partially, through the generation of ROS, and thus this report strengthens the powerful application of proteomics in the study of the pathogenesis of M. pneumoniae.

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