iTRAQ-based proteomics analysis reveals the deregulated proteins related to liver toxicity induced by melamine with or without cyanuric acid in mice.

The administration of melamine alone or its combination with cyanuric acid was shown to have certain liver toxicity. However, the injury mechanism of melamine-related toxicity to liver remains poorly understood. In the present study, we investigated the deregulated proteins related to liver toxicity induced by melamine with or without cyanuric acid in mice using iTRAQ quantitative proteomics technique. A total of 166 proteins were significantly changed by the melamine treatment, of which, 36 proteins were up-regulated and 130 proteins were down-regulated. Whereas, 242 proteins were significantly changed by the combined treatment of melamine and cyanuric acid, of which 81 proteins were up-regulated and 161 proteins were down-regulated. The enriched analysis of GO terms and KEGG pathway on the altered proteins showed that both enriched main GO terms and KEGG pathways appear to be different between the two kinds of treatments: melamine and mixture of melamine and cyanuric acid. Based on western blotting technique, it was confirmed that the expression of three proteins: heat shock protein 70 (HSP70), protein disulphide isomerase 6 (PDIA6) and heat shock 70 kDa protein 4-like (HSPA4L) were agreement with the findings in iTRAQ-Based quantitative analysis. These identified proteins might participate in the regulation of a wide range of biological processes, such as immune and inflammatory function, unfolded proteins response in endoplasmic reticulum, DNA damage, and the apoptosis of liver cells. These results from this study provide a new way to gain insight into the mechanisms of melamine-related toxicity to liver in animals.