title: p,p'-Dichlorodiphenoxydichloroethylene induced apoptosis of Sertoli cells through oxidative stress-mediated p38 MAPK and mitochondrial pathway.
abstract: p,p'-DDE, the major metabolite of dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism underlying its male reproductive toxicity remains limited. Our previous studies have demonstrated that p,p'-DDE could induce mitochondria-mediated apoptosis of cultured rat Sertoli cells. In the present study, we investigated mitogen-activated protein kinase pathways as well as other mitochondria-related molecules including Bax family members and cytochrome c. Results showed that p,p'-DDE could induce oxidative stress-mediated p38 and JNK phosphorylation. In addition, elevated mRNA levels of cytochrome c and ratios of bax/bcl-w and bak/bcl-w were induced by p,p'-DDE treatment, which could be inhibited by RNA synthesis inhibitor (actinomycin D). p,p'-DDE-induced apoptosis was blocked by NAC (N-acetyl-L-cystein) preincubation and attenuated by pretreatment with p38 inhibitor (SB202190) or actinomycin D, but not with JNK inhibitor (SP600125). All of the findings suggested that oxidative stress-mediated p38 MAPK pathway and the balance between pro- and anti-apoptotic bax-gene family might play critical roles in p,p'-DDE-induced apoptosis.
authors.affiliation: MOE Key Lab 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, Hubei, PRChina.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Shi
authors.forename: Haige
authors.initials: H
authors.lastname: Yu
authors.forename: Yafei
authors.initials: Y
authors.lastname: Hu
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.forename: Kedi
authors.initials: K
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000873:Anthracenes; C491072:Bcl2l2 protein, rat; D007093:Imidazoles; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D012333:RNA, Messenger; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D003633:Dichlorodiphenyl Dichloroethylene; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D000111:Acetylcysteine