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Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.ORCID-id: 0000-0001-5751-3622
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
2013 (engelsk)Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, nr 7, s. 1867-1875Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

Conclusion:

The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

sted, utgiver, år, opplag, sider
Cancer Research UK , 2013. Vol. 109, nr 7, s. 1867-1875
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-100305DOI: 10.1038/bjc.2013.525ISI: 000325216700021OAI: oai:DiVA.org:liu-100305DiVA, id: diva2:661514
Merknad

Funding Agencies|Swedish Cancer Foundation|12 0553|Swedish Research Council|12X-07879|

Tilgjengelig fra: 2013-11-04 Laget: 2013-11-04 Sist oppdatert: 2019-02-11bibliografisk kontrollert

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