p,p'-DDE induces mitochondria-mediated apoptosis of cultured rat Sertoli cells.
p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism underlying male reproductive toxicity of p,p'-DDE remains limited. In the present study, Sertoli cells were used to investigate the molecular mechanism involved in p,p'-DDE's male reproductive toxicity. Results showed that p,p'-DDE exposure at over 30 microM showed induction of apoptotic cell death. p,p'-DDE could induce mitochondria-mediated apoptotic changes including elevation in reactive oxygen species (ROS) generation, decrease in mitochondrial membrane potential (DeltaPsi(m)), and release of cytochrome c into the cytosol, which could be blocked by antioxidant agent N-acetyl-l-cysteine (NAC). In addition, elevated ratios of Bax/Bcl-w and Bak/Bcl-w and cleavages of procaspase-3 and -9 were induced by p,p'-DDE treatment. All of the results suggested that ROS generation may play a critical role in the initiation of p,p'-DDE-induced apoptosis by mediation of the disruption of DeltaPsi(m), the release of cytochrome c into the cytosol and further the activation of caspase cascade.
Song
Yang
Y
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China. sygp_0@163.com
Liang
Xianmin
X
Hu
Yafei
Y
Wang
Yinan
Y
Yu
Haige
H
Yang
Kedi
K
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007306:Insecticides / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494774:Bak1 protein, rat; C494828:Bax protein, rat; C491072:Bcl2l2 protein, rat; D007306:Insecticides; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D003633:Dichlorodiphenyl Dichloroethylene; D007770:L-Lactate Dehydrogenase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000111:Acetylcysteine