Induction of proteotoxic stress by the mycotoxin patulin.
Induction of proteotoxic stress by the mycotoxin patulin.
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DOI：
10.1016/j.toxlet.2017.05.015
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发表时间：
2017-07-05
影响因子：
3.5
通讯作者：
Hanna J
中科院分区：
文献类型：
--
作者：
Guerra-Moreno A;Hanna J
棒曲霉素是一种天然存在的霉菌毒素，由许多霉菌产生，可污染多种食品。在实践中，展青霉素的主要社会相关性涉及苹果汁及其产品。包括美国食品和药物管理局（fda）和世界卫生组织（World Health Organization）在内的多个咨询机构建议生产商监测并限制苹果汁产品中的展霉素含量。棒曲霉素的毒性机制仍不甚清楚。本研究表明，展霉素可诱导酿酒酵母的蛋白毒性应激。转录因子Rpn4控制着蛋白酶体的丰度，蛋白酶体是一种复杂的多亚基蛋白酶，可以破坏蛋白质，包括错误折叠的蛋白质。Rpn4蛋白受展霉素的强烈诱导，随着时间的推移，Rpn4水平趋于正常化，符合稳态调节。rpn4Δ突变体对展霉素高度敏感，证实了这种反应的生理相关性。已知Rpn4在转录和翻译后都受到调控。展霉素诱导这两种调节途径，但转录后途径在控制Rpn4蛋白水平方面占主导地位。这些结果表明，蛋白质毒性是展霉素毒性的一个主要方面。它们不仅对棒曲霉素解毒有影响，而且还提出了一些潜在有用的棒曲霉素应用的可能性。
Patulin is a naturally occurring mycotoxin produced by a number of molds and may contaminate a wide variety of food products. In practice, patulin’s main societal relevance concerns apple juice and its products. Multiple advisory bodies, including the U.S. Food and Drug Administration and the World Health Organization, recommend that producers monitor and limit patulin levels in apple juice products. The mechanism of patulin toxicity remains largely unknown. Here we show that patulin induces proteotoxic stress in the yeast S. cerevisiae. The transcription factor Rpn4 controls the abundance of the proteasome, the complex multisubunit protease that destroys proteins, including misfolded proteins. Rpn4 protein is strongly induced by patulin, and Rpn4 levels normalize over time, consistent with homeostatic regulation. A rpn4Δ mutant is highly sensitive to patulin, confirming the physiologic relevance of this response. Rpn4 is known to be regulated both transcriptionally and post-translationally. Patulin induces both pathways of regulation, but the post-transcriptional pathway predominates in controlling Rpn4 protein levels. These results indicate that proteotoxicity represents a major aspect of patulin toxicity. They not only have implications for patulin detoxification but in addition suggest the possibility of some potentially useful patulin applications.
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影响因子：
4.8
作者：
Hanna, John;Waterman, David;Finley, Daniel
通讯作者：
Finley, Daniel
影响因子：
5.1
作者：
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影响因子：
64.5
作者：
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作者：
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