title: Toxic effects of TiO2nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+/PKC/p38 MAPK/NF-κB cascade.
abstract: Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO2NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO2NPs for 24 h, and TiO2NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO2NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration-dependent manner. Furthermore, immunological dysfunction caused by TiO2NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO2NPs significantly decreased Ca2+-ATPase and Ca2+/Mg2+-ATPase activity and enhanced intracellular Ca2+levels, and up-regulated the expression of p-PKC and p-p38 MAPK in a dose-dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO2NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca2+/PKC/p38 MAPK cascade, which triggers NF-κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1374-1382, 2017.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Lingqun
authors.initials: L
authors.lastname: Ye
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ze
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Jiangsu Food and Pharmaceutical Science College, Huaian, 223303, China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
mesh_terms: D000818:Animals; D002118:Calcium / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects* / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D008297:Male; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000276:immunology* / Q000473:pathology; D014025:Titanium / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C009495:titanium dioxide; D014025:Titanium; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium
keywords: immunological dysfunction; nanoparticle toxicity; primary cultured rat sertoli cells; titanium dioxide nanoparticles