Impaired non-homologous end joining in human primary alveolar type II cells in emphysema
Genre
Journal articleDate
2019-01-29Author
Kosmider, Beata
Lin, Chih-Ru
Vlasenko, Liudmila
Marchetti, Nathaniel

Bolla, Sudhir
Criner, Gerard

Messier, Elise
Reisdorph, Nichole
Powell, Roger L.
Madesh, Muniswamy
Kelsen, Steven

Xander, Nathaniel
Correll, Kelly A.
Mason, Robert J.
Bahmed, Karim
Group
Center for Inflammation, Translational and Clinical Lung Research (Temple University)Department
Thoracic Medicine and SurgeryPhysiology
Medical Genetics and Molecular Biochemistry
Permanent link to this record
http://hdl.handle.net/20.500.12613/8381
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https://doi.org/10.1038/s41598-018-37000-zAbstract
Emphysema is characterized by alveolar wall destruction induced mainly by cigarette smoke. Oxidative damage of DNA may contribute to the pathophysiology of this disease. We studied the impairment of the non-homologous end joining (NHEJ) repair pathway and DNA damage in alveolar type II (ATII) cells and emphysema development. We isolated primary ATII cells from control smokers, nonsmokers, and patients with emphysema to determine DNA damage and repair. We found higher reactive oxygen species generation and DNA damage in ATII cells obtained from individuals with this disease in comparison with controls. We also observed low phosphorylation of H2AX, which activates DSBs repair signaling, in emphysema. Our results indicate the impairement of NHEJ, as detected by low XLF expression. We also analyzed the role of DJ-1, which has a cytoprotective activity. We detected DJ-1 and XLF interaction in ATII cells in emphysema, which suggests the impairment of their function. Moreover, we found that DJ-1 KO mice are more susceptible to DNA damage induced by cigarette smoke. Our results suggest that oxidative DNA damage and ineffective the DSBs repair via the impaired NHEJ may contribute to ATII cell death in emphysema.Citation
Kosmider, B., Lin, CR., Vlasenko, L. et al. Impaired non-homologous end joining in human primary alveolar type II cells in emphysema. Sci Rep 9, 920 (2019). https://doi.org/10.1038/s41598-018-37000-zCitation to related work
Nature ResearchHas part
Scientific Reports, Vol. 9, No. 920ADA compliance
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http://dx.doi.org/10.34944/dspace/8348