Lee Won-Young, Lee Ran, Park Hyun-Jung
Department of Livestock, Korea National University of Agriculure and Fisheries, Jeonju-si 54874, Republic of Korea.
Department of Animal Biotechnology, College of Life Science, Sangji University, Wonju-si 26339, Republic of Korea.
Toxics. 2023 Apr 21;11(4):397. doi: 10.3390/toxics11040397.
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.
戊唑醇（TEB）是一种三唑类杀菌剂，用于通过控制真菌、昆虫和杂草来提高作物产量。尽管其被广泛使用，但人们仍担心与杀虫剂和杀菌剂相关的健康风险。许多研究已经明确了农药中三唑基团的细胞毒性，但尚未研究TEB对牛乳腺上皮细胞（MAC-T细胞）的毒性机制。奶牛乳腺受损会直接影响产奶量。本研究调查了TEB对MAC-T细胞的毒理学效应。我们发现，TEB会降低细胞活力和增殖，并通过上调促凋亡蛋白（如裂解的半胱天冬酶3和8以及BAX）来激活凋亡性细胞死亡。TEB还通过上调Bip/GRP78、PDI、ATF4、CHOP和ERO1-Lα诱导内质网（ER）应激。我们发现，TEB通过激活ER应激诱导线粒体介导的MAC-T细胞凋亡性死亡。这种细胞损伤最终导致MAC-T细胞中与乳蛋白合成相关的基因LGB、LALA、CSN1S1、CSN1S2和CSNK的表达水平大幅降低。我们的数据表明，奶牛接触TEB可能会通过损害乳腺对产奶量产生负面影响。
