Journal
REPRODUCTIVE TOXICOLOGY
Volume 52, Issue -, Pages 71-77Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2015.02.007
Keywords
Zearalenone; Endoplasmic reticulum stress; Primary mouse Leydig cells; Murine Leydig tumour cell line; Apoptosis
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Funding
- National Natural Science Foundation of China [31201966]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110204120010]
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Zearalenone (ZEN) is a Fusarium mycotoxin that causes several reproductive disorders and genotoxic effects. This study demonstrated the involvement of endoplasmic reticulum (ER) stress in ZEN-induced mouse Leydig cell death. Our study showed that ZEN reduced cell proliferation in a murine Leydig tumour cell line in a dose-dependent manner. The involvement of apoptosis as a major cause of ZEN-induced cell death was further confirmed by the results of a caspase-3 activity assay, which showed a ZEN dose-dependent increase in cell death. Treatment of MLTC-1 and primary mouse Leydig cells with ZEN upregulated the expression of the ER stress-typical markers GRP78, CHOP and caspase-12 protein. Further, pre-treating the cells with 4-phenylbutyrate or knocking down GRP78 using lentivirusencoded shRNA significantly diminished ZEN-induced apoptosis and inhibited the expression of CHOP and caspase-12. In summary, these results suggest that the activation of an ER stress pathway plays a key role in ZEN-induced apoptosis in the mouse Leydig cells. (C) 2015 Elsevier Inc. All rights reserved.
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