Han John J W, Nguyen Carolyn D, Thrasher Julianna P, DeGuzman Anna, Chan Jefferson Y
Department of Laboratory Medicine and Pathology, University of California, Irvine, D440 Medical Sciences, Irvine, CA 92697, USA.
Department of Laboratory Medicine and Pathology, University of California, Irvine, D440 Medical Sciences, Irvine, CA 92697, USA.
Toxicology. 2022 Apr 15;471:153173. doi: 10.1016/j.tox.2022.153173. Epub 2022 Mar 31.
Patulin is a mycotoxin produced by a variety of molds that is found in various food products. The adverse health effects associated with exposure to patulin has led to many investigations into the biological basis driving the toxicity of patulin. Nevertheless, the mechanisms through which mammalian cells resists patulin-mediated toxicity is poorly understood. Here, we show that loss of the Nrf1 transcription factor renders cells sensitive to the acute cytotoxic effects of patulin. Nrf1 deficiency leads to accumulation of ubiquitinated proteins and protein aggregates in response to patulin exposure. Nrf1 expression is induced by patulin, and activation of proteasome genes by patulin is Nrf1-dependent. These findings suggest the Nrf1 transcription factor plays a crucial role in modulating cellular stress response against patulin cytotoxicity.
展青霉素是由多种霉菌产生的一种霉菌毒素，存在于各种食品中。与接触展青霉素相关的不良健康影响引发了许多关于展青霉素毒性生物学基础的研究。然而，哺乳动物细胞抵抗展青霉素介导毒性的机制仍知之甚少。在此，我们表明Nrf1转录因子的缺失使细胞对展青霉素的急性细胞毒性作用敏感。Nrf1缺乏导致在接触展青霉素时泛素化蛋白和蛋白聚集体的积累。展青霉素可诱导Nrf1表达，展青霉素对蛋白酶体基因的激活是Nrf1依赖性的。这些发现表明Nrf1转录因子在调节细胞对抗展青霉素细胞毒性的应激反应中起关键作用。
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