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Nephrotoxicity is the most prominent of ochratoxin A (OTA) among the diverse range of toxicological effects. Previous work indicated that reactive oxygen species (ROS) play an important role in the pathogenesis of a variety of renal diseases, and its major endogenous source is mitochondria. No research has used global protein expression profiling to investigate potential toxicity mechanisms of OTA at the mitochondria level. An iTRAQ-based mitoproteomics approach was used to explore possible toxicity mechanisms of OTA and potential protective mechanisms of N-acetyl-L-cysteine (NAC) using the mitochondria of Human Embryonic Kidney 293 (HEK 293) cells. Our results showed that OTA induced a decrease in ΔΨm, and an increase in ROS and cell death. We identified a total of 1973 nonredundant proteins, among which 1398 proteins (70.86%) were overlapped. There were 66 significantly different proteins expressed in response to OTA, which were mainly involved in the perturbation of the mitochondrial electron transport chain (mETC), inhibition of protein synthesis, and induction of stress response and cell death. In addition, NAC could almost completely reverse the adverse effects of OTA at the protein level. Finally, a hypothetical model of OTA-induced mitochondria damage is proposed to provide a framework for the toxicity mechanism of OTA.
Pubmed ID: 23088929
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsComputable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsA tool to design target-specific primers for polymerase chain reaction (PCR). It uses Primer3 to design PCR primers and then uses BLAST and global alignment algorithm to screen primers against user-selected database in order to avoid primer pairs (all combinations including forward-reverse primer pair, forward-forward as well as reverse-reverse pairs) that can cause non-specific amplifications.
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