Patulin induces pro-survival functions via autophagy inhibition and p62 accumulation

文献类型： 外文期刊

第一作者： Guo, X.

作者： Guo, X.;Dong, Y.;Yin, S.;Zhao, C.;Huo, Y.;Hu, H.;Guo, X.;Fan, L.

作者机构：

关键词： patulin;autophagy;p62;UPR;bad phosphorylation

期刊名称：CELL DEATH & DISEASE （ 影响因子：8.469； 五年影响因子：8.713 ）

ISSN： 2041-4889

年卷期： 2013 年 4 卷

页码：

收录情况： SCI

摘要： Patulin (PAT) is one of the most common mycotoxins found in moldy fruits. Skin contact is one of the most likely exposure routes of PAT. Investigation of dermal toxicity of PAT is clearly needed and has been highlighted by WHO. In the present study, using human keratinocyte HaCaT cells as a model, we found that treatment with PAT caused an increased autophagosome accumulation. Measurements of autophagic flux demonstrated that the accumulation of autophagosomes by PAT was not directly due to enhanced autophagosome formation but due to inhibition of autophagosome degradation. Reductions in the activities of the lysosomal enzymes cathepsin B and cathepsin D by PAT might contribute to this inhibitory effect. Consistent with this, inhibition of autophagosome degradation by PAT resulted in accumulation of p62 that functioned as a pro-survival signal. The pro-survival function of p62 was found to be attributed to reactive oxygen species-mediated cytoprotective endoplasmic reticulum (ER) stress response. ER stress exerted cytoprotective effect via extracellular signal-regulated kinase1/2-dependent B-cell CLL/lymphoma 2-associated agonist of cell death inhibitory phosphorylation. Given the critical role of autophagy and its substrate p62 in carcinogenesis, our findings may have important implications in PAT-induced skin carcinogenesis.

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