Wollenhaupt K, Jonas L, Tiemann U, Tomek W
Unit of Reproductive Biology, Research Institute for the Biology of Farm Animals, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Reprod Toxicol. 2004 Dec;19(2):189-99. doi: 10.1016/j.reprotox.2004.08.005.
The molecular mechanisms that control the mycotoxin-mediated effects in porcine endometrial cells are far from being completely understood. Recent results show that they could inhibit cell proliferation. Therefore, the present study investigated the effects of the mycotoxins alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) on a cellular level. Mainly, the abundance and phosphorylation state (activity) of the cell cycle-dependent kinases MAPK and Akt (PKB) and their potential targets eIF4E (eukaryotic initiation factor 4E) and 4E-BP1 (4E binding protein, eIF4E repressor protein) were investigated. The results show that alpha-ZOL has apparently only a slight influence on the phosphorylation state of MAP kinases, Akt and on eIF4E and 4E-BP1. In contrast, their phosphorylation was strongly reduced in beta-ZOL-treated cells in a concentration-dependent manner. Therefore, our results indicate that beta-ZOL potentially not only influences transcription but also effects gene expression on translational level. The effect of alpha- and beta-ZOL on endometrial cell proliferation and their toxicology are discussed.
控制霉菌毒素对猪子宫内膜细胞作用的分子机制远未完全明晰。近期研究结果表明,它们能够抑制细胞增殖。因此,本研究在细胞水平上探究了霉菌毒素α-玉米赤霉醇(α-ZOL)和β-玉米赤霉醇(β-ZOL)的作用。主要研究了细胞周期依赖性激酶MAPK和Akt(PKB)及其潜在靶点eIF4E(真核生物起始因子4E)和4E-BP1(4E结合蛋白,eIF4E抑制蛋白)的丰度和磷酸化状态(活性)。结果显示,α-ZOL对MAP激酶、Akt以及eIF4E和4E-BP1的磷酸化状态显然仅有轻微影响。相比之下,在β-ZOL处理的细胞中,它们的磷酸化以浓度依赖的方式显著降低。因此,我们的结果表明,β-ZOL不仅可能影响转录,还会在翻译水平上影响基因表达。文中讨论了α-和β-ZOL对子宫内膜细胞增殖的影响及其毒理学。