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High-Fat Diet Induced Isoform Changes of the Parkinson's Disease Protein DJ-1


Wurst,  Wolfgang
Max Planck Institute of Psychiatry, Max Planck Society;

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Poschmann, G., Seyfarth, K., Agbo, D. B., Klafki, H.-W., Rozman, J., Wurst, W., et al. (2014). High-Fat Diet Induced Isoform Changes of the Parkinson's Disease Protein DJ-1. JOURNAL OF PROTEOME RESEARCH, 13(5), 2339-2351. doi:10.1021/pr401157k.

Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights into the underlying processes involved in energy intake and weight gain, we compared hypothalamic tissue of mice kept on a high-fat or control diet for 10 days by a proteomic approach. Using two-dimensional difference gel electrophoresis in combination with LC-MS/MS, we observed significant abundance changes in 15 protein spots. One isoform of the protein DJ-1 was elevated in the high-fat diet group in three different mouse strains SWR/J, CS7BL/6N, and AKR/J analyzed. Large-scale validation of DJ-1 isoforms in individual samples and tissues confirmed a shift in the pattern of DJ-1 isoforms toward more acidic isoforms in several brain and peripheral tissues after feeding a high-fat diet for 10 days. The identification of oxidation of cysteine 106 as well as 2-succinyl modification of the same residue by mass spectrometry not only explains the isoelectric shift of DJ-1 but also links our results to similar shifts of DJ-1 observed in neurodegenerative disease states under oxidative stress. We hypothesize that DJ-1 is a common physiological sensor involved in both nutrition-induced effects and neurodegenerative disease states.