Comparative Proteomic Analysis of Proteins Influenced by Melanin-concentrating Hormone and Melanin-concentrating Hormone Receptor 2 Interaction

Abstract

Melanin-concentrating hormone receptor 2 (MCHR2), a second G protein-coupled receptor for melanin-concentrating hormone (MCH), has been known for many years. However, its physiological function is poorly understood. To identify the proteins involved in MCHR2 physiological function, a comparative proteomic analysis of protein expression in SH-SY5Y cells stably expressing human MCHR2 (SH-SY5Y-MCHR2) and control SH-SY5Y cells (SH-SY5Y-mock) – both treated with MCH – was conducted. Significant changes were observed in the expression of 34 proteins, including isocitrate dehydrogenase (NAD) subunit alpha, mitochondrial (IDH3A), phosphoenolpyruvate carboxykinase 1 (PCK1), 6-phosphofructo-2-kinase/fructose-2.6-biphosphatase 4 (PFKFB4), insulin-induced gene 2 protein (INSIG2), and acyl-coenzyme A thioesterase 8 (ACOT8). Among the proteins, IDH3A, PCK1, PFKFB4 increased significantly, and INSIG2, ACOT8 decreased significantly in experimental cells compared with control cells; these findings were further confirmed by semi-quantitative RT-PCR and Western blot analysis. The comparative proteome data may provide a valuable clue to further understand MCHR2 physiological function, and several differentially regulated proteins may be used as target proteins for the development of novel drugs.

Key words

melanin-concentrating hormone receptor 2 - SH-SY5Y cells - proteomics - obesity - diabetes mellitus type 2

References

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