title: High-fat diet induced isoform changes of the Parkinson's disease protein DJ-1.
abstract: 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, C57BL/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.
authors.affiliation: Heinrich-Heine-Universität Düsseldorf , Molecular Proteomics Laboratory, Biomedizinisches Forschungszentrum (BMFZ), Düsseldorf, Germany.
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.forename: Katrin
authors.initials: K
authors.lastname: Seyfarth
authors.forename: Daniela
authors.initials: D
authors.lastname: Besong Agbo
authors.forename: Hans-Wolfgang
authors.initials: HW
authors.lastname: Klafki
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D059305:Diet, High-Fat / Q000009:adverse effects / Q000379:methods*; D015180:Electrophoresis, Gel, Two-Dimensional; D007031:Hypothalamus / Q000378:metabolism*; D007526:Isoelectric Point; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050177:Overweight / Q000209:etiology / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D054464:Peroxiredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
chemical_list: D015513:Oncogene Proteins; D020033:Protein Isoforms; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1