Uranium induces apoptosis in lung epithelial cells.
Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.
Periyakaruppan
Adaikkappan
A
Environmental Toxicology Program, Department of Chemistry, Texas Southern University, Houston, TX 77004, USA.
Sarkar
Shubhashish
S
Ravichandran
Prabakaran
P
Sadanandan
Bindu
B
Sharma
Chidananda S
CS
Ramesh
Vani
V
Hall
Joseph C
JC
Thomas
Renard
R
Wilson
Bobby L
BL
Ramesh
Govindarajan T
GT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D009942:Organometallic Compounds; C005460:uranyl acetate; D003576:Electron Transport Complex IV; D053148:Caspase 3; D053181:Caspase 8