title: The toxic effects of Bisphenol A on the mouse spermatocyte GC-2 cell line: the role of the Ca2+-calmodulin-Ca2+/calmodulin-dependent protein kinase II axis.
abstract: Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is known to induce male reproductive toxicity in rodents. However, its toxic effects on the germ cells are still poorly understood. It has been proposed that Ca(2+) homeostasis and Ca(2+) sensors, including calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII), play critical roles in spermatogenesis. Therefore, in the present study, we aimed to investigate whether a perturbation in Ca(2+)-CaM-CaMKII signaling was involved in the BPA-induced injury to mouse spermatocyte GC-2spd (ts) (GC-2) cells. Our results showed that BPA (range from 0.2 to 20 μM) induced obvious GC-2 cell injury, including decreased cell viability, the release of mitochondrial cytochrome c and the activation of caspase-3. However, these processes could be partially abrogated by pretreatment with a Ca(2+) chelator (BAPTA/AM), a CaM antagonist (W7) or a CaMKII inhibitor (KN93). These results, taken together, indicate that BPA exposure contributes to male germ cell injury, which may be partially mediated through a perturbation in Ca(2+)/CaM/CaMKII signaling and the mitochondrial apoptotic process.
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, 210009, China.
authors.forename: Changfei
authors.initials: C
authors.lastname: Mao
authors.affiliation: Department of Preventive Medicine, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, 212013, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Huan
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 211199, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000633:toxicity*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D015398:Signal Transduction; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D053148:Caspase 3; D045304:Cytochromes c; D052244:Endocrine Disruptors; D010636:Phenols; C505409:Casp3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; GC-2 cells; apoptosis; calcium; calcium/calmodulin-dependent protein kinase II; calmodulin