Atrazine Induces Endoplasmic Reticulum Stress-Mediated Apoptosis of T Lymphocytes Via the Caspase-8-Dependent Pathway

作者：Lee Eun Jin; Jang Youngsaeng; Kang Kwonyoon; Song Da Hyun; Kim Rihyun; Chang Hee Won; Lee Dong Eil; Song Claire Ka Eun; Choi Bongkun; Kang Min Ji^*; Chang Eun Ju^*

来源：Environmental Toxicology, 2016, 31(8): 998-1008.

DOI：10.1002/tox.22109

• atrazine
• T-cells
• endoplasmic reticulum stress
• apoptosis
• caspase-8

Atrazine (ATR) is one of the most commonly applied broad-spectrum herbicides. Although ATR is well known to be a biologically hazardous molecule with potential toxicity in the immune system, the molecular mechanisms responsible for ATR-induced immunotoxicity remain unclear. In this study, we found that the immunotoxic properties of ATR were mediated through the induction of apoptotic changes in T lymphocytes. Mice exposed to ATR for 4 weeks exhibited a significant decrease in the number of spleen CD3(+) T lymphocytes, while CD19(+) B lymphocytes and nonlymphoid cells were unaffected. ATR exposure also led to inhibition of cell growth and induction of apoptosis in human Jurkat T-cells. Importantly, ATR triggered the activation of caspase-3 and the cleavage of caspase-8 and PARP, whereas it did not affect the release of cytochrome c from the mitochondria in Jurkat T-cells. In addition, ATR activated the unfolded protein response signaling pathway, as indicated by eIF2 alpha phosphorylation and CHOP induction. Our results demonstrate that ATR elicited an immunotoxic effect by inducing ER stress-induced apoptosis in T-cells, therefore providing evidence for the molecular mechanism by which ATR induces dysregulation of the immune system.

• 出版日期2016-8