Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

被引:35
作者
Dong, Guang-Hui [1 ]
Wang, Jing [2 ]
Zhang, Ying-Hua [1 ]
Liu, Miao-Miao [1 ]
Wang, Da [1 ]
Zheng, Li [3 ]
Jin, Yi-He [1 ,4 ]
机构
[1] China Med Univ, Sch Publ Hlth, Shenyang 110001, Peoples R China
[2] St Louis Univ, Sch Publ Hlth, Dept Biostat, St Louis, MO 63104 USA
[3] China Med Univ, Coll Basic Med Sci, Dept Immunol, Shenyang 110001, Peoples R China
[4] Dalian Univ Technol, Sch Environm Sci & Technol, Key Lab Ind Ecol & Environm Engn, Minist Educ, Dalian 116024, Peoples R China
基金
中国国家自然科学基金;
关键词
Perfluorooctane sulfonate; Immunocyte; Apoptosis; Oncoprotein; Mice; CYTOCHROME-C RELEASE; POTASSIUM PERFLUOROOCTANESULFONATE; PERFLUOROALKYL ACIDS; HUMORAL IMMUNITY; SERUM-LEVELS; P53; CELLS; EXPRESSION; CHILDREN; PROTEIN;
D O I
10.1016/j.taap.2012.08.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondria! involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:292 / 299
页数:8
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