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High fat diet induced isoform changes of the Parkinson’s disease protein DJ-1.
J. Proteome Res. 13, 2339-2351 (2014)
Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights in 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 2D 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 the analyzed three different mouse strains SWR/J, C57BL/6N and AKR/J. Large scale validation of DJ-1 isoforms in individual samples and tissues confirmed a shift in the pattern of DJ-1 isoforms towards more acidic isoforms in several brain and peripheral tissues after feeding a high-fat diet for 10 days. The identification of an oxidation of cysteine 106 as well as a 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Dj-1 ; High-fat Diet ; Obesity ; Oxidative Thiol Modification ; Protein Isoforms; Cysteine-sulfinic Acid; Body-mass Index; Alpha-synuclein; 2-dimensional Electrophoresis; Oxidative Damage; Induced Obesity; Swr/j Mice; Spectrometry; Stress; Brain
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Zeitschrift
Journal of Proteome Research
Quellenangaben
Band: 13,
Heft: 5,
Seiten: 2339-2351
Verlag
American Chemical Society (ACS)
Verlagsort
Washington
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed