Methylmercury chloride induces alveolar type II epithelial cell damage through an oxidative stress-related mitochondrial cell death pathway.
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.
Department of Nutrition, College of Health Care, China Medical University, Taichung, Taiwan.
Tien Hui
TH
Lu
Chun Hung
CH
Chen
Ming Jye
MJ
Lee
Tsung Jung
TJ
Ho
Yuk Man
YM
Leung
Dong Zong
DZ
Hung
Cheng Chien
CC
Yen
Tsung Ying
TY
He
Ya Wen
YW
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D008767:Methylmercury Compounds; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; D008315:Malondialdehyde; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; C004925:methylmercuric chloride