title: Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.
abstract: BACKGROUND
  Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain's metabolic control centre.
  
  
  METHODS
  The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia.
  
  
  CONCLUSIONS
  The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Cell Biology, Faculty of Health Sciences, Linköping University, Linköping, S-581 85, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Ihnatko
authors.forename: C
authors.initials: C
authors.lastname: Post
authors.forename: A
authors.initials: A
authors.lastname: Blomqvist
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D002100:Cachexia / Q000378:metabolism*; D004195:Disease Models, Animal; D034284:Dynamin I / Q000096:biosynthesis; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006593:Hexokinase / Q000096:biosynthesis; D007031:Hypothalamus / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000096:biosynthesis; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000096:biosynthesis; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000378:metabolism*; D051137:Selenium-Binding Proteins / Q000096:biosynthesis
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; D051137:Selenium-Binding Proteins; D008748:Methylcholanthrene; D007655:Ketoglutarate Dehydrogenase Complex; D006593:Hexokinase; D034284:Dynamin I; D052066:N-Ethylmaleimide-Sensitive Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D011766:Pyruvate Carboxylase