Increased susceptibility of human small airway epithelial cells to apoptosis after long term arsenate treatment.
Inorganic arsenic (arsenate and arsenite) are well known human carcinogens. Apoptosis is a normal biological process that is involved in regulating cell development and differentiation, and is an important protective response to cell injury. The aim of this study was to determine the long term arsenic effect on human small airway epithelial cells (SAEC) by analyzing two distinct apoptosis-inducing agents, Fas ligand (Fas L), which evokes death receptor-mediated apoptosis, and hydrogen peroxide H2O2, which induces apoptosis mediated by reactive oxygen species (ROS). The SAEC were continuously exposed to 0.5 microg/mL arsenic for 28 weeks, and apoptosis was examined after 24 h treatment with either Fas L or H2O2. SAEC displayed decreased cell viability and increased apoptosis after treatment with Fas L and H2O2, compared to non-arsenic treated control cells. Furthermore, treatment of these arsenic-exposed SAEC with Fas L or H2O2 induced cleavage of the DNA damage recognition protein, poly (ADP-ribose) polymerase (PARP), and the 'effector' caspase, Caspase-3, both canonical indicators of apoptosis. We observed increased phosphorylation of p38, a member of the MAP kinase family, following treatment with Fas L or H2O2. To confirm the involvement of p38 in the regulation of apoptosis we pretreated cells with the p38 kinase inhibitor, SB 203580 and observed a significant decrease in apoptosis.
Wen
Gengyun
G
Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, United States. gw2154@columbia.edu
Partridge
Michael A
MA
Calaf
Gloria M
GM
Meador
Jarah A
JA
Hu
Burong
B
Echiburú-Chau
Carlos
C
Hong
Mei
M
Hei
Tom K
TK
D017209:Apoptosis / Q000187:drug effects*; D001149:Arsenates / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D053222:Fas Ligand Protein / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D001149:Arsenates; D002273:Carcinogens; D053222:Fas Ligand Protein; D004247:DNA; D006861:Hydrogen Peroxide; D053148:Caspase 3; C025657:arsenic acid