title: Atrazine induces endoplasmic reticulum stress-mediated apoptosis of T lymphocytes via the caspase-8-dependent pathway.
abstract: 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 eIF2α 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. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 998-1008, 2016.
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Eun-Jin
authors: EJ
authors: Lee
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Youngsaeng
authors: Y
authors: Jang
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Kwonyoon
authors: K
authors: Kang
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Da-Hyun
authors: DH
authors: Song
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Rihyun
authors: R
authors: Kim
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Hee-Won
authors: HW
authors: Chang
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Dong Eil
authors: DE
authors: Lee
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Claire Ka-Eun
authors: CK
authors: Song
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Bongkun
authors: B
authors: Choi
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Min-Ji
authors: MJ
authors: Kang
authors: Department of Biomedical Sciences, Cell Dysfunction Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.
authors: Eun-Ju
authors: EJ
authors: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001280:Atrazine / Q000633:toxicity*; D053181:Caspase 8 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D056811:Unfolded Protein Response; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D006540:Herbicides; D014874:Water Pollutants, Chemical; D045304:Cytochromes c; C505530:CASP8 protein, human; D053181:Caspase 8; D001280:Atrazine
keywords: T-cells; apoptosis; atrazine; caspase-8; endoplasmic reticulum stress