Mercury, one of the widespread
pollutants in the world, induces oxidative stress and dysfunction in many cell types. Alveolar type II epithelial cells are known to be vulnerable to oxidative stress. Alveolar type II epithelial cells produce and secrete
surfactants to maintain morphological organization, biophysical functions, biochemical composition, and immunity in lung tissues. However, the precise action and mechanism of
mercury on alveolar type II epithelial cell damage remains unclear. In this study, we investigate the effect and possible mechanism of
methylmercury chloride (MeHgCl) on the human lung invasive
carcinoma cell line (Cl1-0) and mouse lung tissue. Cl1-0 cells were exposed to MeHgCl (2.5-10 microM) for 24-72 h. The results showed a decrease in cell viability and an increase in
malondialdehyde (MDA) level and ROS production at 72 h after MeHgCl exposure in a dose-dependent manner.
Caspase-3 activity, sub-G1 contents and
annexin-V binding were dramatically enhanced in Cl1-0 cells treated with MeHgCl. MeHgCl could also activate Bax, release
cytochrome c, and cleave
poly(ADP-Ribose) polymerase (PARP), and decrease
surfactant proteins mRNA levels. Moreover, in vivo study showed that
mercury contents of blood and lung tissues were significantly increased after MeHgCl treatment in mice. The MDA levels in plasma and lung tissues were also dramatically raised after MeHgCl treatment. Lung tissue sections of MeHgCl-treated mice showed pathological
fibrosis as compared with vehicle control. The
mRNA levels of
proteins in apoptotic signaling, including p53, mdm-2, Bax, Bad, and
caspase-3 were increased in mice after exposure to MeHgCl. In addition, the
mRNA levels of
surfactant proteins (SPs), namely, SP-A, SP-B, SP-C, and
SP-D (alveolar epithelial cell functional markers) were significantly decreased. These results suggest that MeHgCl activates an oxidative stress-induced mitochondrial cell death in alveolar epithelial cells.