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J Biomed Mater Res A. 2017 May;105(5):1374-1382. doi: 10.1002/jbm.a.36021. Epub 2017 Feb 24.

Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+ /PKC/p38 MAPK/NF-κB cascade.

Ye L1, Hong F2,3,4, Ze X1, Li L1, Zhou Y5, Ze Y1.

Author information

1
Department of Biochemistry and Molecular Biology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215123, China.
2
Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.
3
Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.
4
Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
5
Jiangsu Food and Pharmaceutical Science College, Huaian, 223303, China.

Abstract

Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) 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 TiO2 NPs 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 TiO2 NPs for 24 h, and TiO2 NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO2 NPs 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 TiO2 NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO2 NPs 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 TiO2 NPs 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.

KEYWORDS:

immunological dysfunction; nanoparticle toxicity; primary cultured rat sertoli cells; titanium dioxide nanoparticles

PMID:
28188686
DOI:
10.1002/jbm.a.36021
[Indexed for MEDLINE]

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