Proteomic Differential Display Analysis Reveals Decreased Expression of PEA-15 and Vimentin in FABP7-Deficient Astrocytes

Abstract

Fatty acid binding proteins (FABPs) are intracellular lipid chaperones which mediate the uptake, transportation and signaling roles of fatty acids. Former studies suggest that FABP7 regulates proliferation and differentiation of radial glia and astrocytes and is associated with various central nervous system diseases including glioma and neuropsychiatric diseases. However, the underlying mechanism is poorly understood. To further explore the mechanistic roles of FABP7 on astrocyte function, the proteome of astrocytes cultured from Fabp7 KO mice was compared with wild-type counterparts by two-dimensional gel electrophoresis (2-DE). We found that 16 protein spots showed differential expression intensity on 2-DE gels. Among them, seven spots appeared elevated, and nine spots appeared decreased in Fabp7 KO astrocytes. Selected spots were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis and their protein identity was subsequently revealed using protein databases. Four spots including phosphoprotein enriched in astrocytes 15 (PEA-15), GFAP, vimentin and FABP7 were selected for further confirmation by Western blotting. Consistently, there was a significant decrease in expression of PEA-15 and vimentin, both of which play significant roles in proliferation, differentiation, maturation, and survival of astrocytes. These results suggest the molecular mechanism how FABP7 controls astrocyte function and provide new insight to explain the role of FABP7 in glioma and reactive gliosis.