Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines

Abstract

Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups in pesticides, but the mechanisms of TEB toxicity in bovine mammary gland epithelial cells (MAC-T cells) have not yet been studied. Damage to the mammary glands of dairy cows directly affects milk production. This study investigated the toxicological effects of TEB on MAC-T cells. We found that TEB decreases both cell viability and proliferation and activates apoptotic cell death via the upregulation of pro-apoptotic proteins, such as cleaved caspases 3 and 8 and BAX. TEB also induced endoplasmic reticulum (ER) stress via the upregulation of Bip/GRP78; PDI; ATF4; CHOP; and ERO1-Lα. We found that TEB induced mitochondria-mediated apoptotic MAC-T cell death by activating ER stress. This cell damage eventually led to a dramatic reduction in the expression levels of the milk-protein-synthesis-related genes LGB; LALA; CSN1S1; CSN1S2; and CSNK in MAC-T cells. Our data suggest that the exposure of dairy cows to TEB may negatively affect milk production by damaging the mammary glands.