Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells.
Deregulated apoptosis has been associated with many lung diseases. Although many studies have reported the apoptotic effects exhibited by silver nanoparticles (Ag-NPs) in various circumstances, the apoptosis mechanism of Ag-NPs is unclear. We investigated oxidative stress and apoptosis in human normal bronchial epithelial (BEAS-2B) cells to elucidate the role of p53 in apoptosis by Ag-NPs. First, dispersion and stability of Ag-NPs improved using bronchial epithelial cell growth medium with 5% fetal bovine serum. Then, we observed oxidative stress in BEAS-2B cells exposed to Ag-NPs. Second, we carried out a cell death assay to measure DNA fragmentation as a biomarker of apoptosis. BEAS-2B cells were treated with p53-specific short interfering RNA (siRNA) or p53 inhibitor (pifithrin-α) to investigate whether p53 is involved in apoptosis by Ag-NPs. As a result, Ag-NPs significantly enhanced DNA fragmentation dose-dependently and treatment with p53 siRNA or pifithrin-α prevented DNA fragmentation. We also found that apoptosis-related genes (caspase-3, Bax, and Bcl-2) were regulated by Ag-NPs, which was detected by mRNA and protein levels. These results suggest that Ag-NPs induced p53-mediated apoptosis in BEAS-2B cells. Our findings may contribute to understanding the potential roles of Ag-NPs in pulmonary disease.
School of Pharmacy, Sungkyunkwan University.
Ha Ryong
HR
Kim
Da Young
DY
Shin
Yong Joo
YJ
Park
Chang We
CW
Park
Seung Min
SM
Oh
Kyu Hyuck
KH
Chung
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D052160:Benzothiazoles / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced; D053768:Metal Nanoparticles / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering; D012834:Silver / Q000009:adverse effects*; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D052160:Benzothiazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014050:Toluene; D012834:Silver; C121565:pifithrin; D053148:Caspase 3