Abstract
Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and fruit-based products. Previous work indicated that PAT-induced apoptosis in which reactive oxygen species (ROS) are involved in human embryonic kidney (HEK293) cells. To uncover novel aspects of the possible mechanism of PAT nephrotoxicity, the transcriptome and proteome profiles were investigated using the digital gene expression (DGE) and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approaches. A total of 127 genes and 85 proteins were found to express differentially in response to 5 μM PAT for 10 h in HEK293 cells. The most dramatic changes of expression were noticed with genes or proteins related to apoptosis, oxidative phosphorylation ribosome and cell cycle. Especially, the activation of caspase 3, UQCR11, active transport form and endocytosis appeared to be crucial in PAT kidney cytotoxicity. PAT also seemed to be associated with cancer and neuropathic disease as pathways associated with carcinogenesis, Alzheimer’s disease and Parkinson’s disease were induced. Overall, this study served to uncover overall insights associated with signaling pathway that modulated the PAT toxicity mechanism.
Highlights
Patulin (PAT) is a highly toxic secondary metabolite produced by Aspergillus sp. and Penicillium sp., it can be commonly found in rotten fruits and crops as well as their derivative products [1,2]
Several of the differentially expressed genes and proteins were functionally disease-associated, especially associated with carcinogenesis, Alzheimer’ disease and Parkinson’s disease. These findings provide support that PAT seemed to be associated with cancer and neuropathic disease
Our results implied that the dysfunction of electron transport chain, especially the elevated expression of UQCR11 might be able to explain the increase of reactive oxygen species (ROS)
Summary
Patulin (PAT) is a highly toxic secondary metabolite produced by Aspergillus sp. and Penicillium sp., it can be commonly found in rotten fruits and crops as well as their derivative products [1,2]. Patulin (PAT) is a highly toxic secondary metabolite produced by Aspergillus sp. At present, controlling PAT contamination remains a huge challenge. The accumulation of PAT presents a food safely risk and health hazard to human. PAT can cause edema, hemorrhage, immune dysfunction and exhibits nephrotoxic, hepatoxic, carcinogenic, neurotoxic and genotoxic properties [3,4]. A variety of mechanisms have been conducted for how PAT works, including forming covalent adducts with essential sulfhydryl groups [5], leading to mitochondrial dysfunction and endoplasmic reticulum stress [6], and the induction of excessive reactive oxygen species (ROS), which induce oxidative DNA damage and membrane peroxidation [7,8,9]. Mitogen-activated protein kinase and P53, Bcl family members as well as autophagy were reported involved in PAT toxicology [10,11]
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